- Absorption - Distribution - Metabolism - Excretion

Introduction to toxicology and heavy metals FINAL TEST Flashcards by Cutler Frandsen

What is the study of the adverse effects of a chemical, physical, or biological agent on living organisms or the ecosystem, including physiological, occupational, environmental, or ecological setting known as?

-Toxicology

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What is the ability of a material to damage a biological system, cause injury, or impair physiological function known as?

-Toxicity

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What is something that can cause harm?

-Hazard

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What is the chance, or probability that harm will occur from and exposure to a specific hazard known as?

-Risk

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What are the two routes of exposure?

Systemic

- Local

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What is the quantity of the toxicant known as?

-Dose

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What is always a the first step in treatment?

Minimizing/eliminating expsoure

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What are the two types of duration of exposure?

Acute

- Chronic

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What is ADME?

Absorption
Distribution
Metabolism
Excretion

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What does ADME deal with?

-Pharmacokinetics

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What is Pharmacokinetics?

-Study of what the body does to the drug or other substance

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What is pharmacodynamics?

-What the drug does to the body

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What are two ways that clearance occurs?

Metabolized into other chemicals that may or may not be active
Elimination (often the kidneys)

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What is 1st order kinetics?

-Under normal conditions, elimination of most drugs/chemicals is proportional to their plasma concentration

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What is zero order kinetics?

-Once saturated, the rate of elimination can become fixed and more drug will be delivered directly into the circulation in unbound fraction that is not readily able to be metabolized and cleared by renal and hepatic mechanisms

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What is the apparent volume in which a substance is distributed throughout the body?

-Volume of distribution

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If you have a compound with Large volume of distribution what does that imply?

Substance is not easily accessible to purification attempts (Hemodialysis)
in other words, compound with larger Vd’s are more difficult to remove vs those with smaller Vd’s

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What are some examples of large volume of distribution drugs?

Antidepressants
Antipsychotics
Antimalarials
Opioids

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If you have a compound with smaller volume of distribution what does that imply?

-Substance are generally more accessible for purification attempts

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What are come examples of drugs that have small volume of distribution?

Salicylates
Ethanol
Phenobarbital

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What is an accumulation of a contaminant or toxic agent when the administration of the drug exceeds the body’s ability to metabolize and eiminate within one organism over time known as?

-Bioaccumulation

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What is an acquisition of increasing levels of contaminant in higher trophic level organisms such as fish, seal , bear as you move up the food chain known as?

-Biomagnification

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What defines some metals as “heavy”?

-Naturally occurring elements with high atomic weight and a density 5 times greater than water

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What is the top three most toxic substances?

Lead (1)
Mercury (2)
Arsenic (3)

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What do heavy metals interfere with?

-Normal biological processes by competing with normal substrates

T/F the shorter the 1/2 life the less effective is the use of chelators to remove the heavy metal

False | -More effective

Does lead have a physiological value?

-No

What are the primary exposure sources of lead?

- Building materials/construction - Batteries (90%) - Lead pipes - Paint

Why is lead exposure particularly detrimental to young children?

- Their bodies absorb it because Pb competes with Ca, and growing bodies require considerable Ca. - They often eat or suck things containing Pb

Children absorb what percent of lead consumed whereas adults absorb what percent?

- Children Greater than 50% | - Adults 10-15%

What is the half life of lead?

1-2 months

What are the symptoms of lead poisoning?

- Headaches - Neurocognitive deficits - Kidney damage - Basophilic stippling of RBC

What does the basophilic stippling of RBCs imply in lead poisoning?

-Damage to bone marrow

What is the main repository in the body for its lead burden?

-Substitutes for Ca2+ in bone

What are Burtonian lines?

-Lead lines causing a darkening of the gingiva

What is the primary cause of lead toxicity?

-The ability to bind sulfhydryl groups found on many enzymes and cofactors, as well as DNA management, and increasing free radicals

What does lead toxicity interfere with?

Ca2+ use

T/F Lead toxicity can cause anemia as well as immunosupression

True

Lead can cross the BBB and concentrate where?

-Gray matter

Besides the BBB what other important barrier can lead cross?

-THe placenta

What is the most sensitive target organ for lead poisoning and what can it lead to?

- Developing CNS | - Lead to encephalopathy

What is the treatment regiment for lead toxicity, particularly the recommended chelators?

- Remove exposure - Supportive care - Administer a chelator - For severe exposure, combine long-term succimer treatment to remove Pb equilibration from bones to the plasam

What chelators can you administer to treat lead toxicity?

- EDTA - Edetate calcium disodium - Succimer - Unithiol

What does the chelator do when treating lead toxicity?

-Removes Pb from bone slowly and require multiple chelating treatments (has to start with the Pb in the RBCs before it can work on the Pb in the bone)

What is mercury aka?

-Quicksilver

What state is mercury in at room temperature?

-Liquid

What form is mercury primarily used in?

-Methylmercury

What are the primary exposure sources of mercury?

- Fish - Amalgam - Thermometers - Industrial purposes

Is there CDC recognized evidence that amalgam is a problem in dentistry?

What is the mechanisms of mercury toxicity?

- Reacts with selenium | - Inhibits enzymes

What is selenium necessary for?

-Reducing oxidized Vitamin C and E

What heavy metal poisoning can cause gingivostomatitis and acute tubular necrosis?

-Mercury

How is mercury eliminated from the body

- Urine | - Feces

What are the symptoms of mercury poisoning?

- Neurological - Psychiatric - Inflammation of lungs

What is Mad Hatter's disease?

-Chronic mercury intoxication that leads to tremors, psychiatric disturbances, gingivostomatitis depression, memory loss, hallucination, that occurred during the process of curing pelts

From the CDC what conclusions did they say that there was no convincing evidence that quantities of mercury from either of the sources what significantly high enough to cause problems?

- Thimerosal in flu vaccines | - Dental amalgam

What is the treatment regiment for mercury toxicity?

- Remove exposure hazard - Hydrocortisone - Chelating agents

What chelating agents can you use to treat mercury intoxication?

- Dimercaprol (1st choice, not water solube) - Succimer - Unithol

What chelator do you only use for acute exposure to mercury?

-Dimercaprol

What chelator do you use for chronic exposure to mercury?

- Succimer | - Unithol

What do you use hydrocortisone for mercury exposure?

-inhalation exposure

What can chronic use of dimercaprol cause?

-Serious renal toxicity

What are the primary exposure sources of arsenic?

- Industrial contamination | - Groundwater contamination

What is arsenic absorbed through?

- Respiratory mucosa - GI tract - No really through the skin

How is arsenic primary excreted?

-Kidney

What are the symptoms of arsenic poisoning?

- Fatigue - Anemia - Renal failure - Hyperpigmentation - Peripheral neuropathy - Hemolytic on RBC

Where is arsenic carcinogenic at?

- Lungs - Skin - Bladder

What does arsenic do the ROS?

-Increase

What does arsenic bind to, and what does that result in?

- Sulfydryl groups in keratinized tissue where its acts as a depot - Inhibits enzymes

What type of arsenic intoxication is chelators useful for?

-Acute arsenic intoxication

What type of arsenic intoxication are chelators not helpful for?

- Chronic arsenic intoxication | - Acute arsenic gas intoxication

What do you use for acute arsine gas intoxication?

-Blood exchange hemodialysis

What is the mechanism of Cyanide?

- Inhibits cytochrome C oxidase in the electron transport chain - Prevents the cells of the body from getting oxygen and ATP, causing cell death

What is the antidote for cyanide?

-Hydroxycobalamin

Cyanide inhibits cellular oxidation by interfering with what?

-oxidative phosphorylation and it prevents ATP production in cells

does cyanide cause cyanosis?

no, even though it competes with oxygen on hemoglobin

which of the following is not considered a heavy metal: lead, cyanide, mercury, arsenic

cyanide

cyanide is widely used in what industries?

tobacco, paper, plastics, textiles, dyes, etc

___ is plasma cleared per unit time

clearance

why can normal kinetic properties of a drug or toxin change at very high blood concentrations?

-metabolism and protein binding become saturated and elimination becomes a zero order pattern

how does the apparent volume of distribution for a drug or toxin determine the effectiveness of hemodialysis at purifying them from the blood?

-a large Vd implies a substance will not be easily accessible to purification attempts

what are some examples of heavy metals that are considered essential nutrients?

-iron, manganese, and zinc

what percent of lead is absorbed by the lungs from the air?

-50-70%

lead substitutes for calcium in bone and can hang around for years. acute storage is in ___ with a t1/2 of ___

-acute storage is in RBCs with a t1/2 of 20-40 hours

what two things does lead poisoning cause?

-anemia and immunosuppression

what are some possible implications if lead crosses the placenta?

- can reduce IQ in children and cause ADD - developing CNS is a sensitive target for toxicity, and can result in encephalopathy - can be harmful to the immune system

what is the most common cause of mercury poisoning?

-contaminated food

what form of mercury is well absorbed by the lungs, but poorly absorbed by the gut?

-elemental Hg vapor (dust)

what form of mercury is well absorbed by the gut (15%), skin, and lungs?

-inorganic Hg

what form of mercury is extremely well absorbed across the gut, but dermal absorption is poor?

-organic Hg

what 3 patients should you never expose to mercury?

- children - pregnant women - those with allergies

what heavy metal has a garlic taste?

-arsenic

what does acute arsenic poisoning cause?

- vomiting - GI problems - cardiotoxicity

what are the long-term exposure affects of arsenic poisoning?

- anemia - hemolysis - diarrhea