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PHAR300 > L17 Toxicology > Flashcards

L17 Toxicology Flashcards

1
Q

What are the two main aspects of toxicology

A

Basic science and risk assessment

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2
Q

What is the principle of toxicology

A

The dose makes the poison

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3
Q

What are some common toxicants

A

Natural toxins (produced by living systems for self defence)
- Mycotoxins (fungi)
- Phytotoxins (plants)
- Animal toxins

Synthetic toxicants
- industrial chemicals, plastics

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4
Q

What do galanthamines do?

A

Inhibit acetylcholinesterase (enzyme that breaks down acetylcholine in synapses)
Competitive inhibitor

*Organophosphates are also competitive inhibitors

unlike organophosphates, they bind reversibly to the enzyme

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5
Q

What do cardiac glycosides (e.g. digitalis) do?

A

Inhibit Na/K pump, cardiac mycocytes gain Ca which increases contractility and increases risk of arrhythmia

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6
Q

TF: cardiac glycosides can be used to treat heart failures and irregular heartbeats

A

True

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7
Q

What does ricin do?

A

Blocks protein synthesis
B chain binds to cells while A chain inhibits ribosomes

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8
Q

What are the main targets of animal toxins

A

Nervous or cardiovascular system

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9
Q

What is hormesis

A

Hormesis is the change in effect of a drug when moving from low to moderate doses of the drug

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10
Q

What can toxicants move through

A

Water, air, soil

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11
Q

Which drug causes the most human poisoning in North America

A

Analgesics (children are most vulnerable)

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12
Q

TF: polluted air and water are major causes of deaths from toxicants

A

True

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13
Q

Explain how polluted air can lead to toxicity in the body

A

Inhaled particles reach the alveoli where they are absorbed into the blood, then they reach the brain via the olfactory bulb

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14
Q

Explain how toxicants can affect microbiome

A

Swallowed pollutants can be absorbed from the GIT, thus altering microbiome

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15
Q

What are the 3 entry routes to the brain for toxicants

A
  1. Olfactory bulb
  2. Alveoli-blood
  3. GI-direct/microbiome
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16
Q

Order the following 3 in terms of which has the most toxic particles

Upper airways
Deep lung
Alveoli

A

Least to most: alveoli < deep lung < upper airways

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17
Q

TF: bioavailability does not vary with location

A

False

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18
Q

Name one way biomagnification can occur

A

Through the food chain

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19
Q

What are 6 measurements for toxicology

A

LD50, TD50, threshold, NOAEL, LOAEL, hormesis

*NOAEL=No observed adverse effect level
LOAEL=lowest observed adverse effect level

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20
Q

What is LD50, TD50, ED50, therapeutic window and therapeutic index

A

LD50 = dose that kills 50% of population

TD50 = dose that causes 50% of the population to be sick

ED50 = dose that causes therapeutic effect in 50% of the population

Therapeutic window is the dose range of a drug that provides safe and effective therapy with minimal adverse effects.

Therapeutic index quantifies the relative safety of drug i.e. distance between toxic/lethal dose and the therapeutic dose (LD50/ED50 or TD50/ED50)

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21
Q

What is NOAEL and LOAEL

A

NOAEL: highest data point (dose) at which there was not an observed toxic or adverse effect - No Observed Adverse Effect Level

LOAEL: lowest data point (dose) at which there was an observed toxic or adverse effect - Lowest Observed Adverse Effect Level

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22
Q

What is threshold?

A

Threshold dose is the minimum dose of drug that triggers minimal detectable biological effect in an animal

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23
Q

What is epidemiology

A

Studies that are conducted in humans to understand toxicants in different areas of the world

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24
Q

What are cohort studies (observational study) and the two methods used for monitoring?

A

A cohort of people who share certain characteristics are studied to compare disease occurrence - exposed and non-exposed groups

  1. prospective study: two groups are monitored for some time, it is accurate but expensive
  2. retrospective study: two groups are looked at at one point in time in the past to see which one has a disease, it is less accurate but faster
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25
Q

What is a case control study (observational study)

A

Compare people who have a certain disease with those who do not, always retrospective

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26
Q

TF: case control studies are always prospective studies

A

False, they are always retrospective

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27
Q

What are cross sectional studies

A

Cross-sectional studies are similar to cohort studies, but they only collect data from one point in time or over a short period. They can identify potential risks or causes for disease, but they are unable to examine whether something causes disease over a longer period.

e.g. population census

Goal: correlate different health problems with all the data collected

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28
Q

What are odds ratio and standard mortality ratio

A

odds ratio: risk of disease in exposed group vs non-exposed group
e.g. if OR = 2, the exposed group is twice as likely to develop the disease

SMR: relative risk of death based on comparison of an exposed and non-exposed group
e.g. SMR = 120, the exposed group has a 20% greater risk of death compared to the non-exposed group

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29
Q

What is relative risk

A

RR: relative risk of disease comparing exposed and non-exposed group
e.g. RR = 175, exposed group has 75% increased risk to contract disease

similar to OR or SMR

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30
Q

What is the difference between risk assessment vs risk management

A

Both are used to characterize risk, but

risk assessment = dose-response assessment, hazard identification, exposure assessment

risk management = control decision, determination of the acceptable risk level, control alternative

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31
Q

What are some subcategories for toxicology

A

forensics, ecotoxicology, specialization in species, organ systems, herbicides, etc.

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32
Q

What does toxicology study

A

it studies the adverse response in biological systems caused by chemical or physical agents

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33
Q

Who said “The dose makes the poison”?

A

Paracelsus

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34
Q

TF: We can characterize something as toxicant without knowing the dose-response curve

A

False we must know what the curve looks like

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35
Q

TF: Most of plant life is toxic

A

True

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36
Q

What kinds of toxins do fungi produce: phytotoxins or mycotoxins?

A

mycotoxins

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37
Q

What kinds of toxins do plants produce?

A

phytotoxins

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38
Q

Why can digitalis/foxglove plant be used as medicine?

A

at small doses it is effective in treating cardiac problems as it contains cardiac glycosides

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39
Q

TF: Toxins can act as agonists or antagonists on receptors (e.g. nicotinic receptors)

A

True

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40
Q

TF: Daffodils are poisonous

A

True

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41
Q

Explain how daffodils are toxic

A

Galantamine is found in daffodil bulbs, it is a competitive inhibitor of acetylcholinervse (which breaks down ACh in synapse). This causes the synapses to flood with ACh, which can paralyze you since the nAChR are always bound causing constant depolarization of the muscle - open blocked receptors

Calcium oxalate crystals are found in the stems, which can cause irritation

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42
Q

How are lilies of the valley toxic?

A

they contain glycerine poison, as well as at least 20 poisonous glycosides, which affect the cardiovascular system. These glycosides can cause cardiac arrhythmia and stop the pumping action of the heart

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43
Q

Name some examples of plants that contain glycosides

A

lily of the valley
oleander

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44
Q

How did cardiac glycosides get their name

A

they have a glycone (sugar portion)

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45
Q

Why are oleanders toxic?

A

they contain high concentrations of cardiac glycosides (inhibit Na-K pump, increase Ca inside cell, increases contractility and arrhythmia)

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46
Q

In what can we find ricin?

A

castor oil beans

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47
Q

Describe the structure of ricin

A

2 components: A and B (functional group/moiety) linked by disulphide bond (thus held tgt by disulphide bridge)

Part B allows Part A to enter the cells and disrupt protein synthesis

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48
Q

TF: An adult will be dead a few minutes after consuming a castor oil bean

A

True, the beans are very potent meaning the Letha dose is ~1mg for an adult

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49
Q

TF: There are no harmful compounds found in foods such as apples, pears, potatoes, and courgettes

A

False, they contain small amounts of harmful substancces

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50
Q

What poison do apple seeds contain

A

amygdalin

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51
Q

TF: mycotoxins and phytotoxins can cause cancer

A

True

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52
Q

What is the term used to refer to animal toxins

A

zootoxins

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53
Q

TF: computers contain a variety of toxic substances

A

True, though they are usually released when discarded

54
Q

Why is it important to bring old electronics to indicated collection sites?

A

toxins from old electronics can leak into soil and water, which can spread. Some toxins get into the air and are deposited elsewhere

55
Q

Why does poisoning mostly occur in children

A

Up until the age of 5, children are most vulnerable as they are unaware of the thins they are consuming

56
Q

Other then during childhood, what other stage of life is vulnerable to deaths by poisoning?

A

Adolescence and adulthood (they are experimenting with drugs)

57
Q

TF: large amounts of salt, saturated fats, and additives can be viewed as toxins

A

True, and it can be worse than the toxins found on the surface of the food you buy

58
Q

Why is it important to consider acute and chronic toxicity?

A

Some substances do not have adverse acute effects, but my cause serious problems in the long term (e.g. alcohol)

59
Q

Why is it more difficult to assess long-term toxic effects?

A

It is more difficult to link chronic toxicity to low exposure over a long time (e.g. arsenic)

60
Q

TF: Although toxins can affect male and female fertility, they do not affect the fetus

A

False, the fetus is also affected

61
Q

What are the 3 major ways we’re exposed to pollution?

A

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

62
Q

What do pollutants mainly affect?

A

CV and nervous system
+GI tract which is sensitive

63
Q

What is enteritis

A

inflammation of the small intestine

64
Q

TF: In developed countries, it is more common to be harmed by pollutants in water than in air

A

False, air pollutants are usually more harmful than water pollutants (in developed countries)

65
Q

What are some current toxicant exposure problems? (5)

A

tobacco smoking, secondhand smoking, air pollution, ambient particulate matter, coal burning

66
Q

TF: There are more deaths associated with acute poisoning than with chronic toxicity

A

False, chronic toxicity is linked to more deaths

67
Q

Fine particles found in gases and in the air can damager what? How?

A

heart, lungs, brains (affect all major organ systems)

the smaller particles that are not trapped by mucus go down into the distal airways (where they are phagocytose by alveolar macrophages)

however, ultra-fine particles can diffuse right through the alveoli and into the capillaries (where it is transported to the rest of the body like the brain)

68
Q

TF: There is no evidence demonstrating impaired development in children living in highly polluted areas

A

False, there is. Though there is no evidence linking dementia to pollution

69
Q

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

A

nasal-sinus region in the olfactory bulb
lungs and blood
swallowing air -> GIT (+microbiome) and blood

70
Q

What is an important concept for environmental toxicology?

A

The environment in which the toxicant is present affects how much of it can be absorbed

e.g. pH and flow rate of water affects how much of the toxicant is available ti be absorbed - collective group of toxicants (air, water, soil) must also be considered

71
Q

How can the bioavailability of a toxin vary with location?

A

build up of sediment can affect the food chain (from filter feeders to apex predators) i.e. biomagnification - concentration can can get up to 10 million times its initial concentration in water

72
Q

Biomagnification has caused the endangerment of what species (specific example)

A

Canadian loon

73
Q

Which is the deadliest form of food poisoning and why?

A

Botulinum toxin (LD50 = 0.0001 mg/kg)

74
Q

TF: Botulinum toxin can be found in canned food and is used for botox

A

True

75
Q

TF: The smaller the LD/ED ratio, the safer the drug

A

False, a larger difference would indicate a safer drug

76
Q

What are 4 examples of toxicants that don’t have beneficial roles in humans and can be lethal in very small doses?

A

botulinum toxin (bacteria)
strychnine sulfate (pesticide)
rattlesnake venom
nicotine

77
Q

TF: Ethanol is considered safe due to it’s large therapeutic index

A

False, ethanol’s LD50 and ED50 are actually quite close to each other

78
Q

Which is better to consider when administering a drug, TD50 or LD50?

A

TD50 because we want to avoid troublesome side effects

79
Q

TF: most toxins can have therapeutic effects

A

False, both TD50 and LD50 are considered

80
Q

Why are dose response curves important when considering toxicants even if they do not show potential for therapeutic effects?

A

To find out their toxic threshold (dose at which toxic effects appear) or if any dose is toxic

Doing so allows us to decide whether government action must be taken to determine permissible dose of that toxicant

81
Q

TF: nicotine taken in low doses does not pose any toxic effects?

A

False, nicotine does not have a safe dose
Although acutely there are no effects, chronic use shows dangerous adverse effects

82
Q

TF: Drugs above the safer threshold are considered safe

A

False, drugs under the threshold are considered safe

Generally False, but digitalis for example would be true

83
Q

TF: Carcinogens possess a safety threshold

A

False, they do not

84
Q

TF: Anything in between NOAEL and LOAEL is considered safe

A

False, anything in between is unknown and require further study

anything under NOAEL is safe
anything under LOAEL is safe

*NOAEL = No observed adverse effect level
*LOAL = Lowest observed adverse effect level

85
Q

TF: LOAEL is considered to be the safety threshold

A

False, NOAEL and LOAEL both consists of different thresholds used to determine the safety threshold

86
Q

TF: It is possible to overdose on vitamins

A

True, vitamins can be harmful at high concentrations (hormesis)

87
Q

Is it possible for small amounts of an otherwise beneficial substance to cause harmful effects/be toxic

A

Yes, small doses of antimicrobial drugs can cause AMR and increase bacterial growth rate

High doses simply eliminate the bacteria

88
Q

Is the following a display of hormesis: Prostate cells in tissue culture secrete androgens at the same levels despite changes in pesticide concentration

A

No, as there is no change in effect (androgen release) due to change in doses of pesticide

This statement is also false, since at higher levels of pesticide, prostate cells release lower levels of androgens

89
Q

TF: Animals used for research and educational purposes comprise the largest proportion of animals killed per year

A

False

90
Q

TF: There are strict regulation for animal treatment in research and normal products

A

False, there are no regulations against animal cruelty in products sold

91
Q

Why is warfarin used to kill rats? How does it work

A

It is a relatively painless death compared to glue traps. It causes internal bleeding as it is an anticoagulant

92
Q

TF: cohort studies are exposure->outcome, case control studies are outcome->exposure, and cross-sectional studies are outcome->exposure

A

False for cross-sectional studies, which relate exposure and outcome at the same time

93
Q

What is the difference between bias and confounding

A

Bias = non-representative/misclassification due to preconceived ideas

Confounding = factors that researched didn’t control for e.g. smoking in participants is not controlled for

94
Q

TF: Conducting a prospective study minimizes the risk of confounding compared to retrospective studies

A

True, retrospective studies cannot control confounding factors as easily since there is not regular monitoring over time

95
Q

Governments make decisions on which substances to ban based on what kinds of studies?

A

epidemiological studies

96
Q

What group of people is most vulnerable to lead contamination and why?

A

children since there are more susceptible to lower doses and they put things in their mouths

though adults are also affected

97
Q

What are the main targets for lead contamination

A

CV system, nervous system + sensitivity in kidneys, GIT

98
Q

Lead contamination can be considered _ _ in children because it leads to impairment of _ _, _, _

A

developmental toxicity

impairment of intellectual development, hearing, and growth

99
Q

TF: Lead contamination does not affect fetuses

A

False, it can cross the placenta and thus affect the fetus

100
Q

TF: Lead is biodegradable

A

False

101
Q

Why do pipes in older homes need to be checked?

A

Paint used in 1950s used to contain lead which could have contained/accumulated in water pipes

102
Q

What are symptoms of lead poisoning?

A

short-term: psychological and mental changes, GI issues, fatigue irritability, CNS/neurological effects, joint/ankle/wrist effects

103
Q

Why is lead contamination so dangerous in children

A

Lower doses can cause brain, hearing, nerve damage, impaired intellectual functions, digestive issues and stunted growth

104
Q

Lead used to be found where?

A

gasoline, paint, plumbing

105
Q

Why where children who lived near highways more susceptible to having lower IQs?

A

Lead found in gasoline affected brain development

106
Q

What are the pharmacodynamic effects of lead?

A

Lead alters the function of calcium and zinc (divalent cations), thus affecting ion channels (neurotransmitter release) and many proteins

calcium signalling is blocked, NMDARs are blocked, mGLURs are affected, mitochondria and gene transcription are affected

End result: CNS is heavily affected

NMDAR are ligand-gated ion channels while mGLUR are g-protein coupled receptors. NMDAR are highly reliant on calcium

107
Q

TF: lead inhibits ion channels only

A

False, lead can stimulate or inhibit ion channels depending on location and circumstances

108
Q

What are some specific consequences on the CNS for children affected by lead poisoning?

A

smaller prefrontal cortex
impaired synaptogenesis
apoptosis of neurons
hyperexcitability

109
Q

Why is are the pharmacokinetics of lead so complex?

A

it can be taken up from the soil, air, water, paint, dust - absorbed by the lungs and GIT

Lead gets stored in the bones, which can then later be mobilized

110
Q

Where can mercury be found?

A

volcanoes, pollution from industries (anthropogenic) where it moves to soil, water, air

mercury becomes more toxic in soil and water is it becomes methyl mercury

111
Q

Why does methyl mercury bioaccumulate?

A

it is not biodegradable

112
Q

What are short term effects and long term effects of mercury poisoning?

A

short: memory loss, impaired hearing, vision, speech, tremors, lack of coordination, skin issues, difficulty chewing and swallowing

long: weakness, fatigue, anorexia, weight loss, disturbed GIT function, deteriorated nervous system

113
Q

What is the Grasshopper effect

A

When seasons change, air masses that rose from hotter regions of the planet move north and deposit their contaminants as the air cools down

This repeats with every season change, contaminants move further North

Once up North, bioaccumulation occurs and there is magnification of mercury in Northern wildlife

114
Q

What are 3 kinds of pesticides

A

insecticides, herbicides, pesticides

115
Q

What mechanisms of action can pesticides use?

A

inhibit cell division, protein synthesis

herbicides aren’t super toxic but they can cause irritation

carotenoid synthesis/photosynthesis may be affected but are not targets

116
Q

Why has the use of insecticides been so beneficial in the realm of human disease?

A

By eliminating ticks, lice, and fleas, there is less disease transmission (e.g. malaria, yellow fever, plague, etc.)

Over 30 human diseases have been decreased

117
Q

What constitutes an ideal pesticide? (4)

A
  1. minimal/very low toxicity
  2. auto degraded/little persistence in environment
  3. little risk to non-target organisms (specific)
  4. Does not confer resistance
118
Q

TF: pesticides harm different species in an equivalent manner

A

False

e.g. trout are resistant to parathion, but not rats

119
Q

How can the use of pesticides in crops spread?

A

the runoff from fields gets into streams, groundwater, rivers, and the ocean

120
Q

Why are lipophilic chemicals dangerous

A

they accumulate in body fat

121
Q

TF: Pesticides are overall very toxic to humans

A

False, although some can be absorbed through the skin, most are not super toxic

122
Q

What is the half-life for DDT (organochlorine/insecticide)

A

10 years

123
Q

Why was DDT so useful during WW1?

A

It warded many insects that transmit various disease such as lice and mosquitoes

124
Q

Why did people stop using DDT?

A

The constant use of DDT caused bioaccumulation, which made bird eggshells more fragile. This resulted in a decrease in bird population (“A Silent Spring” book was a turning point)

125
Q

What is the mechanism of action of organochlorines

A

They act on voltage gated sodium channels

126
Q

Why are insects so vulnerable to organochlorines?

A

Insects were sensitive to the action on voltage gated sodium channels, causing hyperexcitability (channels are open for longer) which lead to death

127
Q

What is Lindane and how does it work

A

An pesticide/insecticide that works by blocking inhibition in bugs like termite (GABA receptors) which lead to convulsions in insects

128
Q

What are Pyrethroids and how do they work? Which insects would they act on

A

They are insecticides derived from plants that act on voltage gated sodium channels, thus increasing hyperexcitability leading to death

lice, ticks, fleas

129
Q

Name 3 kinds of insecticides

A

Organochlorines (act on VGSC voltage-gated sodium channel)
Pyrethroids (“)
Organophosphates (ACh breakdown inhibitor)

130
Q

What is the mechanism of action of organophosphates?

A

they irreversibly inhibit acetylcholinesterase which is responsible for breaking down ACh

Death is due to respiratory failure

131
Q

What is Malathion and how does it work

A

It is a manmade organophosphate that is least toxic to animals (enzyme that can metabolize it)

It causes death by excess stimulation of nicotinic receptors by ACh

132
Q

Which one is an organochlorine? and organophosphate?

Lindane
Malathion

A

lindane = organochlorine
malathion = organophosphate

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