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Pharm 2 > Intro Toxicity > Flashcards

Intro Toxicity Flashcards

(53 cards)

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1
Q

How are tests done on animals?

A

-ingestion, skin application, inhalation, gavage
-placing the product in water or air of test animal’s environment

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2
Q

What does cruelty-free mean?

A

-there are no laws surrounding the statement
-could mean the final product is not currently being tested on animals, but the separate ingredients probably have been

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3
Q

what are some measures of toxicity?

A

-mortality
-teratogenicity (causes birth defects)
-carcinogenicity (cause cancer)
-mutagenicity (causes heritable change in DNA)

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4
Q

How is toxicity measured?

A

-as clinical “endpoints”

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5
Q

What is LD50?

A

-median lethal dose
-dose where 50% of the population would die
-expressed in mg/kg

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6
Q

What is the definition of poison?

A

-any pesticide with LD50 of 50mg/kg or less
-must have labels
-must have “danger” and “poison”
-must have skull with crossbones

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7
Q

What are the LD50 of some insecticides?

A

-nicotine = 50mg/kg
-TCDD (dioxin) = 0.1mg/kg
-parathion = 13 mg/kg
-malathion = 370 mg/kg

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8
Q

What are heavy metals?

A

-chemical elements with specific gravity less than 5x specific gravity of water
-atomic weight greater than Na and density greater than 5 g/cm^3
-high reflectivity, electrical/thermal conductivity, strength
-usually includes lead, cadmium, mercury

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9
Q

How are metals absorbed through the respiratory system?

A

-vapor or aerosol
-readily absorbed in alveolar space
-larger particles cleared via mucociliary transport and swallowed
-small particles may reach gas exchange and can be absorbed into blood

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10
Q

how are metals absorbed into the gastrointestinal tract?

A

-through food or water
-absorbed in GI tract lining via diffusion, transport or pinocytosis

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11
Q

What are some factors that change the absorption of heavy metals in the GI tract?

A

-metal solubility
-chemical forms of metal (methyl mercury is lipid soluble vs inorganic mercury isn’t)
-similar composition = similar absorption sites (calcium & lead)
-physiological state of the person (ex. vit d increases lead abs.)

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12
Q

Which heavy metals are readily absorbed in alveolar space?

A

-cadmium
-mercury
-tetraethyl lead

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13
Q

How are heavy metals excreted from the body?

A

-metals in blood can be bound to plasma proteins and AA
-if bound to low MW proteins and AA = filtered in glomerulus into fluid of renal tubule
-Cd and Zn can be reabsorbed in the tubule

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14
Q

Can enterohepatic circulation occur with heavy metals?

A

-yes
-absorbed metal may be excreted into bile, pancreatic secretions, or saliva

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15
Q

What are some minor pathways of excretion for heavy metals?

A

-hair (Hg, Zn, Cu, As)
-nails
-saliva
-perspiration
-exhaled hair
-lactation
-exfoliated skin

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16
Q

What is the acute toxicity of metals?

A

-pt not usually exposed and suddenly gets exposed to it
-from high-concentration exposure with little opportunity to detoxify, eliminate, or adapt

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17
Q

How is acute toxicity of metals treated?

A

-increase elimination
-prevent irreversible organ/tissue damage
-treat symptoms

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18
Q

What is the chronic toxicity of metals?

A

-more problematic because you cannot tell that it’s occurring until it has accumulated over time
-diagnosed by finding excessive metals in blood and urine
-organs not involved in abs or elim of metals may also be affected

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19
Q

What are the similarities and differences between acute and chronic metal toxicity?

A

Difference: the time between exposure and symptoms is different, organs affected is different
Similarities: treatment and most symptoms

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20
Q

Where can lead be found and lead to exposure?

A

-outdoor paint products (lead in residential paint banned in 1977)
-soil
-dust
-paint chips
-contaminated water
- lead-related occupation
-folk remedies
-congenital exposure

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21
Q

What are the two lead types still used in some countries?

A

-tetraethyl lead
-tetramethyl lead
-found in gasoline

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22
Q

What are the kinetics and dynamics of lead in the body?

Study These Flashcards
A

Abs:
-Lungs: if small enough
-GI: children abs more than adults
-Skin: organic lead well abs
Distribution: bound to RBC, goes to bone, teeth, liver, lung, brain (crosses BBB), placenta, etc.
Excretion:
-kidney: 30ug-200ug/day
-feces

23
Q

Which type of lead is better absorbed through the skin?

Study These Flashcards
A

-organic lead is well-absorbed
-inorganic lead is not well absorbed

24
Q

Acute vs chronic lead toxicity clinical manifestations

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A

-acute tox: causes acute encephalopathy, renal failure, and severe GI symptoms
-chronic tox: lead has an affinity for SH groups and toxic to zinc-dependent enzyme systems
-uses the same channels in the heart as other ions

25
What are some systems that are affected by chronic metal toxicity?
-heme synth: -steroid met and membrane integrity -interferes with vit D synth in renal tubular cells
26
What Vit D synthesis rxn is affected by chronic metal toxicity?
conversion of 1-hydroxyvitamin D to 1,25-hydroxyvitamin D
27
What are the two main effects of lead toxicity?
-when lead levels increase in the blood they cross the BBB and cause cellular and neurological effects
28
What is the pathway for cellular effects from lead toxicity?
-cellular effects -> hormone activates G protein -> opens Ca channel -> ER release of Ca -> lead enters cell via Ca channels -> binds with calmodulin -> inflam, met, apoptosis, muscle contraction, improper immune stimulation
29
What is the pathway for the neurological effects of lead toxicity?
-neurological effects -> disrupts astrocytes and endothelial -> plasma moves into interstitial space -> increased intracranial pressure -> edema, encephalopathy, irreversible brain damage
30
What is the MOA of lead?
acts as a substitute to other bivalent cations like Ca2+, Mg2+, Fe2+ and monovalent cations like Na+
31
Where can mercury be found?
-three forms: elemental, inorganic salts, organic -mining, smelting and industrial discharges = contamination -can convert to organic mercury via bacteria in fish -organic more toxic than inorganic -found in thermometers, light bulbs, disc batteries
32
What are the effects of elemental mercury?
-acute necrotizing bronchitis, pneumonitis, death -long term: early-stage -> insomnia, forgetfulness, anorexia, mild tremor late-stage -> progressive tumor, erethism, salivation, renal toxicity -dental amalgams *do not* pose risk
33
What are the effects of inorganic mercury?
-GI ulceration and hemorrhage -breakdown mucosal barriers -*Acrodynoa*: pink disease; from dermal exposure; maculopapular rash and swelling
34
What are the effects of organic mercury?
-CNS effects: paresthesias, weakness, tremor, coma and death -Tetrogen effects: asymptomatic mothers give to child = retardation, blindness, deafness, seizures
35
What is the plausible pathway for ethyl mercury toxicity?
-mercury preservative -> ethyl mercury -> goes to brain and decreases glutathione -> neuroinflammation and oxidative stress = increases free radicals -> encephalopathy
36
Why do bigger fish have more mercury than smaller fish?
-because bigger fish eat all the smaller fish and smaller organisms that contain mercury and the mercury accumulates -food chain
37
What are the biological effects of mercury?
-CNS = neuropsychiatric (tremor, insomnia, depression), sensorimotor (loss of senses, incoordination, paralysis =degrades neurons and disrupts met -Kidney = tubular damage from inorganic Hg -Others = stomatitis, gingivitis, excess salivation
38
How is mercury toxicity diagnosed and treated?
-diagnosis made in lab -inorganic mercury can be measured in 24h of urine -organic mercury can be measured in blood -treatment includes ending exposure; chelating agents enhance elimination
39
What drug increases mercury concentration in the brain?
dimercaprol
40
How are artificial sweeteners measured?
-on a sweetness scale relative to sucrose -sucrose = 1
41
What are some artificial sweeteners and their sweetness?
-saccharin = 300x -sucralose = 600x -aspartame = 180x
42
What is saccharin?
-non-carb -not metabolized by the body for energy -discovered on accident -human studies show safe -findings found cancerous bladder tumors in rats = controversial -epigenetic/promoter -causes cell proliferation after high doses and long exposure
43
What does GRAS stand for?
generally recognized as safe -prof says bullshit statement
44
What is aspartame?
-non-carb -aspartic acid with phenylalanine and methyl ester -dipeptide intermediate -also discovered on accident -does not satisfy cravings -met into AA used for tyrosine synthesis, excess phenylalanine -> fumarate and acetoacetate for energy met
45
What products contain aspartame?
-breath mints -soft drinks -cereals -gum -candy -ice creams -drinkable yogurt
46
What are the safety concerns with aspartame?
-formaldehyde poisoning (methanol converts into formaldehyde -formaldehyde = severe damage to the immune system, NS and genetic damage
47
Why do artificial sweeteners not satisfy sugar cravings?
-because they send false signals to the brain and when the body doesn't receive the carbohydrates, the brain sends more signals -this leads to increased cravings
48
what is acesulfame potassium?
-sweetener -200x sweeter than sucrose
49
What is the ADI of acesulfame K set by the FDA?
-15mg/kg -less than the amount that people take every day
50
What are some issues with acesulfame K?
-lack of long-term studies because FDA has not required them -contains carcinogen methylene chloride -methylene chloride can lead to mental confusion, liver effects, visual disturbances, and cancer
51
what is sucralose?
-aka Splenda -newest sweetener -no calories -given GRAS -FDA states non-carcinogenic and no neurological risk -ADI = 5mg/kg
52
What are some risks with sucralose?
-has chlorine = carcinogenic -lack of long-term studies -study found rats had half the amount of good bacteria
53
What was the proposed accurate name for sucralose?
trichlorogalactosucrose

Pharm 2 (11 decks)

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