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PHAR 300 > L17: Toxicology > Flashcards

L17: Toxicology Flashcards

1
Q

What is the study of toxicology?

A

Toxicology is the study of the adverse responses in biological systems caused by chemical or physical agents.

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2
Q

What are the 2 basic functions of toxicology?

A
  1. Basic science: Study the nature and mechanisms of adverse effects
  2. Risk assessment: assess the likelihood of the occurrence of adverse effects
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3
Q

What kind of toxins do fungi produce? Plants?

A

Fungi produce mycotoxins

Plants produce phytotoxins

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4
Q

What is the effect of biological toxins on nicotinic receptors?

A

Some are agonists and some are antagonists. Too much of one extreme (blockage or stimulation) of nicotinic receptors is lethal.

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5
Q

What poisons do Daffodils contain?

A

Galantamine and Lycorine.

Calcium oxalate crystals are found in the stems of daffodils, which are irritating.

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6
Q

What is Galantamine?

A

Galantamine is a competitive inhibitor of acetylcholine esterase which breaks down acetylcholine. By blocking the breakdown of acetylcholine, the synapse can be flooded with acetylcholine which can paralyze you since your nicotinic acetylcholine receptors are always bound by acetylcholine and thus your muscles are always depolarized and you cannot choose when to activate them to move. Your receptors stay open and blocked so your muscles are blocked.

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7
Q

What does Atropine do?

A

A cholinergic blocker that acts in the parasympathetic nervous system.

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8
Q

What plant are glycosides found in? What do glycosides do?

A

Oleander. Lily of the valley has at least 20 poisonous glycosides in it. Glycosides affect the cardiovascular system and can cause cardiac arrhythmia and stop the pumping mechanism of the heart which can be lethal.

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9
Q

What is Ricin?

A

Poison found in castor oil beans.
There are two components of ricin: an A and B moiety. Part A is active it disrupts protein synthesis and Part B allows ricin to enter the cell and bind to the cell surface. The two parts are held together by a disulfide bridge. An adult consuming one bean will be dead in a few minutes since you cannot produce proteins.

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10
Q

Explain “The dose makes the poison”

A

Just because a chemical is present does not mean that it is harmful in the amounts present.

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11
Q

What are the different natural toxins? What does it cause/target?

A
  1. Mycotoxins: can cause cancer
  2. Phytotoxins: can cause cancer
  3. Animal toxins: target most vulnerable systems = CV and nervous system
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12
Q

What are man made toxins?

A

Toxins that humans release into the environment.

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13
Q

Why is it important to recycle electronics at designated collection sites?

A

Electronics contain a variety of toxic substances in small amounts that may not be dangerous when we use it but when all the electronics accumulate in landfills the toxins can accumulate. The toxin can then gradually leak into soil and water and easily spread to different places. Some gets into the air and travels in air currents and some gets deposited with rain someplace else.

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14
Q

What are the substances most frequently involved in human poisoning and death?

A

Mostly drugs that are not used properly or are not hidden from children properly.

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15
Q

Which age groups are the most at risk of posoning?

A
  1. Children under 5 yrs old.

2. Adolescents/early-adulthood

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16
Q

Why can unhealthy diets be considered a toxin?

A

The large amounts of salt, saturated fats, and calories can be viewed as toxins because they’re fueling a horrific worldwide pandemic of obesity. It kills more than the toxins on the surface of the food you buy. This is why people should be less worried about washing the pesticides off of the products they get from the store and more worried about the unhealthy food they’re eating.

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17
Q

What is the difference between acute and chronic toxicity?

A

Acute:
- Easier to link toxicity to effects.
Chronic:
- Harder to link toxicity to effects because it’s hard to associate the effects of a low level exposure over a long period of time.

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18
Q

How does toxicity affect the unborn?

A

Toxicants can affect male and female fertility as well as the fetus.

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19
Q

Is pollution considered a toxicant?

A

Yes.

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20
Q

What are the three major ways we are exposed to pollution?

A

Air, water, and soil (soil contaminants can get into water and air).

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21
Q

What are the health effects of pollutants?

A

They can affect just about everything in the body, but mainly the cardiovascular and nervous system. We are sensitive in the GI tract, which can cause nausea or enteritis (inflammation of small intestine) due to pesticides, for example.

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22
Q

Why do fine particles present in air need to be considered?

A
  • Because they damage the heart, the lungs, and the brain.
  • Larger particles get trapped on the mucociliary blanket and can be more easily eliminated.
  • Smaller particles get down to the distal airways and are phagocytosed by alveolar macrophages.
  • The ultra-fine particles can diffuse right through alveoli and into the capillaries. They can get transported throughout the body, including the brain.
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23
Q

What are the impacts of fine particles on the brain? The GI tract?

A

Brain: Evidence of impaired development in children living in highly polluted areas.
GI tract: Some of the fine particles end up in the GI tract where they can be absorbed into the bloodstream and can affect the microbiome. The microbiome is known to be very important and an affected microbiome can have an impact on the brain.

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24
Q

What are the routes of entry for fine particles into the brain?

A
  • Nasal sinus region through the olfactory bulb
  • Through the lungs-> alveoli->blood…
  • GI tract by swallowing air
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25
Q

What is an important concept of environmental toxicology in terms of toxicant absorption?

A

The environment in which the toxicant is present affects how much of it can be absorbed. For example, the pH of water and the flow rate of water affects how much of the toxicant is available to be absorbed. We also need to consider the collective group of toxicants in the air, soil, and water.

26
Q

Explain how the bioavailability of a toxin varies with the location due to biomagnification.

A

A contaminant washed into the water builds up in sediments at the bottom. Freshwater mussels at the bottom are filter feeders, so they accumulate the toxins. Then fish eat shellfish that have accumulated these toxins and humans and other animals eat these fish so toxicants go up the food chain and get magnified.

27
Q

When is a toxicant considered a poison?

A

When something is toxic at very low doses.

28
Q

What is LD 50? TD50? Therapeutic index? Margin of safety?

A

LD 50: dose that kills 50% of the population
TD50: dose that causes 50% of the population to have toxic effects
Therapeutic index: Distance between the toxic/lethal dose and the therapeutic dose (LD50/ED50 or TD50/ED50)
Margin of safety: LD01/ED99. The larger, the safer the drug

29
Q

Why is it important to generate dose response curves for different toxicants?

A

We need to have dose response curves for different toxicants to be able to see if they have a toxic threshold or if any dose is toxic. If there is no threshold than any dose is toxic for example carcinogens such as nicotine. We can use these curves to determine whether there needs to be governmental action taken and to determine the permissible dose of that toxicant.

30
Q

Do carcinogens have toxicity threshold?

A

No, there is no safe dose, you want no exposure to them.

31
Q

What are the 2 terms associated with the toxic threshold? Define them.

A
  1. NOAEL: The highest data point at which you see no adverse effects of a substance, anything below is safe.
  2. LOAEL: The lowest data point at which there are observed adverse effects of the substance, anything above is harmful.
  3. In between 1&2: Unknown and further studies are necessary
32
Q

What is hormesis? Give examples.

A

A change in the effect of a drug when you move from low to moderate doses of the drug,

  1. Vitamin: At lower doses of vitamins, there is a positive effect, because they’re good for you. But the curve slope changes to negative past a certain dose. An overdose of vitamins can be harmful.
  2. Antimicrobial: If you take too low a dose of an antibacterial drug, you can promote the development of resistant bacteria and increase their growth rate. At higher doses, you will eliminate the bacteria that make you sick, which is good.
  3. The study of an effect of pesticides on prostate cells shows that the secretion of androgens from cells is high at low doses of the pesticide and decreases as the dose increases.
33
Q

What is Epidemiology?

A

Observational studies conducted on humans to measure the risk of illness or death in an exposed population compared to that risk in an identical, unexposed, control population. (Same age, sex, race, geographical area, environmental and lifestyle influences).

34
Q

What are the 3 different ways to conduct observational studies within epidemiology?

A
  1. Cross sectional surveys
  2. Cohort studies
  3. Case control studies
35
Q

What is a cross sectional survey?

A

You start with a defined population and you collect data on everything like what diseases they have, what they do for a living, what they’re exposed to, Etc. You then try to see what they have in common. The classical example is a population census. The census is a questionnaire that asks people questions pertaining to their Health, occupation, Hobbies, demographics, what they’re exposed to, Etc. This data collected from millions of people goes into a computer system that will correlate different health problems with exposure to different things.

36
Q

What is a case control study?

A

You take people with a certain disease and try to find out the cause so you ask them what they have been exposed to and you try to find what is common to all of these people. Compare them to a control group which is the cases without the disease. It’s a retrospective study. What was one group exposed to that the other one was in?

37
Q

How are the results in the observational studies expressed? Explain them.

A
  1. Odds ratio: The risk of disease in the exposed group divided by the non-exposed group. An odds ratio of two means the expose group is twice as likely to develop the disease.
  2. Standard mortality ratio: The relative risk of death based on a comparison of an exposed to a non-exposed group. Standard mortality ratio (SMR) of 150 indicates the exposed group has a 50% greater risk of death compared to the non-exposed group.
  3. Relative risk: Similar concept as standard mortality rate but you’re looking at the risk of the disease rather than the risk of death. For example of RR of 175 means a 75% increase in Risk.
38
Q

Why is there variation between epidemiological study results? Explain.

A
  1. Bias: People are looking for a certain result, so they’re biased in selecting participants for the study. They have preconceived ideas.
  2. Confounding: A factor that the researchers didn’t control for or account for. For instance, if smoking is not controlled, one group may have more smokers and thus higher instances of heart and lung diseases. Then the researchers May conclude the diseases are caused by the toxic agent when it is actually the cigarettes.
  3. Chance: The researchers did try to control for the demographics of the sample groups, but the demographics were not identical.
39
Q

What are the different types of bias? Explain them.

A
  1. Selection bias: When the study group is not representative of the population from which it came.
  2. Information bias: Occurs when study subjects are misclassified as to disease or exposure status. Recall bias occurs when individuals are asked to remember exposures or conditions that existed years before.
  3. Confounding factors:
    Occur when the study and control population differ with respect of factors which might influence the occurrence of the disease. For example, smoking might be a confounding factor and should be considered when designing studies. Worse for retrospective studies.
40
Q

What is health risk assessment?

A

The process by which the potential adverse health effects of human exposure to etiologic agents usually chemicals are characterized.

41
Q

How is a risk characterized?

A
  1. Hazard identification
  2. Dose response assessment
  3. Exposure assessment
42
Q

What is hazard identification?

A

What adverse effects do the agents cause, if any? Epidemiological, toxic, medical, physical science, biological studies.

43
Q

What is dose response assessment for?

A

necessary to know if the toxic agent is safe at low doses or never safe.

44
Q

After a risk is characterized, who is responsible for managing the risk?

A

The government agencies. They need to decide whether it is serious enough to invest in or not.

45
Q

Who is most affected by lead poisoning? What are the main targets?

A

Both children and adults are affected by lead but children are more vulnerable. The main targets are the cardiovascular system, the nervous system, the kidneys, and the GI tract. Children are more susceptible to lower doses, so there’s big concerns on the brain and growth and the kidneys.

46
Q

Who is most affected by lead poisoning? What are the main targets?

A

Both children and adults are affected by lead but children are more vulnerable. The main targets are the cardiovascular system, the nervous system, the kidneys, and the GI tract. Children are more susceptible to lower doses, so there’s big concerns on the brain development, growth, hearing, and the kidneys. Lead can cross the placenta and affect the fetus.

47
Q

What are the short term lead symptoms? Long term?

A

Short term symptoms: Irritability, psychological and mental changes, GI issues, fatigue
Long term: CNS effects, neurological symptoms, effects on joints (especially ankles and wrists).

48
Q

What caused a significant decrease in lead poisoning in children?

A

The ban of lead in gasoline and paint.

49
Q

What are the pharmacodynamics of lead?

A

Lead Alters the function of many divalent cations, mainly calcium and zinc, affecting ion channels and many proteins. Lead can stimulate and inhibit ion channels depending on the location and the circumstances. It blocks calcium signalling, blocks NMDA receptors, has an effect on metabotropic glutamate receptors, can affect mitochondria and gene transcription because it can enter the cells.
In children, they’re prefrontal cortex will be smaller, they will have impaired synaptogenesis, apoptosis in neurons, hyper-excitability, etc.
Conclusion: there’s effects on the CNS, the brain.

50
Q

Describe the pharmacokinetics of lead.

A

The pharmacokinetics of lead is very complex because it can be taken up from all around us by the dust, air, soil, paint, water. It can be absorbed from the lungs and the GI tract and is widely distributed in the body. It takes a long time to eliminate lead from the body because it gets stored in bone. It can take many years before it comes out of bone. It can also be suddenly mobilize from bone.

51
Q

Where does mercury come from? What is the more toxic compound?

A

Released from volcanoes, various industries. When mercury becomes methylated in water and on land, it becomes methyl mercury, which is more toxic.

52
Q

What is the grasshopper effect?

A

Air rises in the hotter regions of the planet. When the seasons change, air masses move north and as the temperature cools down contaminants are washed down onto the ground and settle. With the next season change, contaminants evaporate into the air and are carried along air masses further north. When contaminants get up north like in the Arctic, you see the classical bioaccumulation of these contaminants going up the food chain. There is magnification of mercury in Northern wildlife. Persistent organic pollutants can also have a grasshopper effect.

53
Q

What are the side effects in humans, of herbicides?

A

Skin irritation.

54
Q

Why are insecticides beneficial?

A

Because they have decreased human diseases because they. kill the insects that carry disease such as mosquitos, ticks, lice , and fleas.
They need to be used safely and they need to be contained to the crops they are on. Don’t want them to get into the wild-life to kill all kinds of creatures.

55
Q

What makes a pesticide ideal?

A
  1. Very low toxicity to anything other than insects
  2. Little or 0 persistence in environment
  3. Little risk to non-target organisms
  4. Little development of resistance. by insects
56
Q

Why do we have to be cautious of the pesticides used on crops?

A

Because run-off from fields get into streams, ground water, rivers, then oceans. Contaminants can also evaporate and get into the air.

57
Q

What is DDT? What is its history?

A

An organochlorine insecticide that saved many people from insect transmitted diseases. It eventually got into the environment and bioaccumulated, and birds became incredibly vulnerable. It didn’t kill birds but it made their egg shells more fragile. The bird population started to decline in regions where DDT was used because their egg shells were breaking and the babies would not survive. DDT is now banned in most developed countries and great care has to be used with any kind of insecticide. Birds are fine now.

58
Q

What do organochlorines act on (pharmacodynamics)?

A

They act on voltage gated sodium channels by causing hyper-excitability because the channels are open for longer. Insect channels are different than human channels and they are more vulnerable.

59
Q

What is Lindane?

A

It’s a pesticide that works by blocking inhibition (GABA receptors) in bugs like termites. It causes convulsions in insects.

60
Q

What are Pyrethroids? What do they act on?

A

An insecticide extracted from the pyrethrum plant. It affects the ion channel by prolonging the opening of the voltage gated sodium channels which increases hyper-excitability in the insect as it increases sodium channels opening. They eventually die.
Ex: insecticides used to kill head lice (safe for humans superficially on head)

61
Q

What are organophosphates? Give an example.

A

They are a type of insecticide that blocks the breakdown of acetylcholine by blocking acetylcholine-esterase irreversibly, like galantamine in daffodils. Leads to death by respiratory failure.
Ex: Melathion: least toxic to mammals because we can break it down very efficiently

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