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PHAR 300 > Toxicology > Flashcards

Toxicology Flashcards

1
Q

What is toxicology

A

Science of poisons - big field

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2
Q

What does toxicology study

A

Adverse responses in biological systems caused by chemical or physical agents
Not just humans

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3
Q

What are the 2 basic functions of toxicology

A

Basic science = Study nature and mechanisms of adverse effects
Risk Assessment = likelihood of occurrence of adverse effects

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4
Q

What did Paracelsus say

A

Dose makes the poison
Too much of anything is bad

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5
Q

What are mycotoxins

A

Produced by fungi
Natural toxin

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6
Q

What are phytotoxins

A

Produced by plants
Almost all plants toxic

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7
Q

What are venoms

A

Produce by animals
Insects, sea creature, to defend themselves

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8
Q

What are neurotoxicants

A

Largest category made by living creatures that make toxins
Also many synthetic toxins
Act on nervous system

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9
Q

Describe neurons

A

Largest cells in body, head—>toe
Nervous system v vulnerable
Structural and functional futures make them vulnerable to toxins

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10
Q

What do neurons do

A

High energy requirement = VM, atonal transport (conduct electricity, pump ions, releasing transmittters at nerv ending)

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11
Q

Describe biological toxins

A

Plants and animals,
To defend themselves selves
Or attack = snake

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12
Q

What is the target of many toxins - biological toxins

A

Nicotinic receptor
Many sites where toxin can act, stimulate or block
Nicotine = stimulate
Snake = antagonist

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13
Q

Describe what happens when block acetylchonlinesterase

A

Inactivation of ach
Many toxins can block = end up with spastics paralysis

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14
Q

What is the target of many plant toxics

A

Post synaptic enzymes = acetylcholinesterase
Daffodil bulbs toxic and snowdrop = contain toxin called galantamine = competitive inhibitor acetylcholineraste
(Potential drug option)

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15
Q

Describe ways to study effects of potential toxins

A

Grow motor neurons
Cortical cultures
Human induced pluripotent stem cells
Astrocytes
Cerebral organoid= study drugs in lab, grow neurons and interactive features with neurons, astrocytes etc = more info what they will do

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16
Q

Majority of plant toxins can act on what

A

Neuro or cardiac toxins = taxing, atropine, lycorine

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17
Q

What are cardiac glycosides

A

Found in plants
Potent cardio toxic ants

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18
Q

Name plants with cardiac glycosides

A

Lily of the valley = at least 20 glycosides
digitoxin
Many common garden plants have it

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19
Q

Describe heart

A

Cardiac myocyte
High energy requirement - contract all the time = electrical (potential diff across cells), mechanical (effort of contraction)
Low energy reserve = cells not very big, no huge energy store
Must work continually = all the time forever

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20
Q

How do cardiac glycosides work

A

Block na-k pump
So cardiac myocyte gains calcium
Increases contractility= more forceful
Risk of arrhythmia, more calcium and less proton pump
Toxicity = conduction system
Lowers pacemaker activity and condition velocity, promotes ectopic impulse generation = get arrhythmia

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21
Q

How to name cardiac glycosides

A

Sugar portion = glycone
Aglycone portion = toxic end, R defines class

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22
Q

Describe oleander

A

Popular plant
One leaf will kill you
A couple will kill a horse
Has high cocentration glycosides
Oleandrin and other glycosides

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23
Q

What are house plants

A

Often poisons
Kalanchoes- cardiac glycosides
Children and pets vulnerable

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24
Q

What is ricin

A

In castor oil beans
2 units = a moiety (enzymatically active toxin) and b moiety (binds to cell surface), linked by disulfide

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25
Q

Describe ricin more specifically

A

A moeity = inactivates Ribsomes, disrupts protein synthesis, can bind to many types of cells
Cells die v quickly since need to highly turn over all components
One of most lethal toxins

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26
Q

What are man made toxins

A

Toxins human release into environment
Affect many systems
Interfering with nervous system, calcium signalling, neuroendocrine, epignetic control

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27
Q

Describe what can be Lund in electronic waste

A

Neurotoxic mixtures
Millions dumped into landfills = accumulate

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28
Q

What happens when computers discarded

A

Toxin leaches in to soil and water
Volatilization = to air and now circulate

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29
Q

Describe substances most frequently involved in human poisoning

A

Drugs - accidental overdose
Number of opioid deaths increasing
Toxins at home
Young children’s aged 1-3 = most vulnerable, until 5

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30
Q

Describe acute vs chronic toxicity

A

Difficult to see long term effects
To link chronic toxicity to a low level exposure over long period of time as opposed to acute toxicity

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31
Q

Describe air pollution

A

Can affect body
Water, soil and air pollution

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32
Q

What is most voluenarble to pollution

A

Heart, lungs, brain

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33
Q

Describe air pollution

A

Breath in small particles all the time

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34
Q

Describe how far down in lungs diff types of particles go - >5um

A

Trapped in upper airways - bc mucus, muociliaey escalator traps particles - swallow and get rid

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35
Q

Describe how far down in lungs diff types of particles go - 1-5um

A

Smaller they get = the further they go
Deep lung deposition

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36
Q

Describe how far down in lungs diff types of particles go - <1um

A

Reach pulmonary alveoli
Through diffusion -through wall

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37
Q

Describe how far down in lungs diff types of particles go - 500nm

A

Phagocytoses by alveolar macrophages = can get rid but some can espace macrophages and go into blood

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38
Q

What can air pollution do to brain

A

Impaired dev - children
Dementiah

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39
Q

How can air pollution get into brain

A

Lungs, swallow, absorb from gi, olfactory bulb

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40
Q

Describe diesel

A

Full of ultra fine particules —> emitted at high levels from exhaust of cars

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41
Q

Describe environmental cardiology

A

Analyze effects of what we breath in affects cvs
Fine particles were more strongly linked with deaths from cardiovascular causes than with deaths from respiratory causes

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42
Q

Describe Canada air

A

86% of Canadians live in areas where air pollution exceeds who 2021 guidelines
Concerned about small particles
Big problem west
2021= who reduced pm 2.5 risk guideline from 10-5ug/m^3

43
Q

Describe micro particles

A

Act on heart, vessels and inner action
Autonomic nervous system imbalances
Systemic oxidative stress and inflammatory response, myocardium
Risk of heart attack - acute mi, cerebrovascular accident = stroke, chronic atherosclerosis - plaque in blood vessels and brain

44
Q

Describe cardiac organoid

A

Mixture of cells that have pacemaker activity = beat as same pace of heart
Convenient and rapid

45
Q

What do nanopartciles do

A

Reach circulation, cause atehrosclerosis

46
Q

What is stenosis

A

Lumen = diameter decreased
Severe before symptoms occur, will not know, wont feel it, can trigger blood clot

47
Q

Describe air pollution - stats

A

> 15 000 deaths/year from short and long term exposure
70% due to cardio and cerebreovascular disease

48
Q

What can stenosis casue

A

Variable consequences, thrombus, embolus = occludes vessels, hemorrhage - if breaks due to wall damage from plaque
Abnormal spams

49
Q

What happen when occlusion in coronary artery

A

20% of people —> sudden death, heart goes into fibrillation

50
Q

Describe stroke

A

Can have direct plug in brain
Or clot forms in heart and can go to brain - pumped to brain

51
Q

Describe enviroemtal toxicology

A

Things we exposed to in wate,r soil and air
Try to make regulations

52
Q

What does environment affect

A

Potential absorption
Ex = humans sometimes will be exposed, sometimes wont be exposed

53
Q

Describe bioavailability of toxin

A

Varies with location
Ex= humans eat fish, fish eat shell fish with toxin, <—toxin in water

54
Q

Describe biomagnification of ddt

A

Concentration magnifies as go up each step in biological food chain, issue for bird species
Water —> producers —> small fish —> large fish —> fish eating birds

55
Q

What is ld50

A

Kill 50% of pop
Botulinum toxin = 0.0001 - small amount v toxic

56
Q

What do we want between ed50 and ld50

A

Far apart
Most of the time work out ld10 (Animals) or td50 in humans to ed50
Do not want desire effect and toxic effect to have parallel curves

57
Q

What do we want in toxicity dose response curve

A

Want it to be safe at low doses
Must see - cause some drugs are not
Is there a threshold — some do not have, so safe dose, like for carcinogens
Caffeine has threshold

58
Q

What is NOAEL

A

HIGHEST data piny at which there was not an abserved toxic or adverse effect
No observed adverse effect level

59
Q

what is LOAEL

A

Lowest data point at which there was an observed toxic or adverse effect
Lowest observed adverse effect level

60
Q

What is hormesis

A

Change in effect of a drug when you mode form low to midterm doses of drugs
Vitamins at lower doses = bad
Antimicrobial drug = little = toxic, promotes growth of bacteria, but at high dose = good
Pesticides - difference depending on dose

61
Q

Describe animal testing

A

Largest proportion of animals killed = food
Then roadkill
V small portion for research purposes = strict regulations for animal tremanet in research

62
Q

Is there regulations against animal cruelty in products sold

A

NOOOOO
Glue traps = horrible
MONTREAL RAT problem = warfarin used, will bleed internally = dies, painless tho

63
Q

What is epidemiology

A

Conducted studies in humans to understand toxic ants in diff areas of world = to see what health problems they have

64
Q

Describe observational studies

A

2 pops = Measure risk of illness or death in exposed pop vs one that is not exposed
3 types = cohort studies,cross sectional studies, case control studies

65
Q

Describe Cohort studies

A

Cohort= group of individuals with exposure to a chemical and a groep without exposed followed over time to compare disease
Ex= ppl living near chemicals vs ppl in same counter but not exposed

66
Q

Describe cohort studies = types

A

Retrospective= compare previous exposures cheaper and faster, collect all data and also how long they have been exposed for —> disease/no disease
Prospective study = compare future exposures more reliable, measure then monitor groups —> diseases/no disease

67
Q

Describe case control studies

A

Cases with disease
Cases without disease
Compare previous exposures
Ask them questions - always retrospective
Can find common issue

68
Q

Describe cross sectional study

A

National census
Computer will find links
Begin with defined pop, gather data on exposure and disease

69
Q

Summarize studies

A

Cohort = exposure —> outcome
Case control = outcomes —> exposure
Cross sectional study = exposures and outcome at same time

70
Q

What is odds ration (o/r)

A

Odds Ratio: The risk of disease in the exposed group vs. the non-exposed group (O/R of ‘2’ means the exposed group is twice as likely to develop the disease)

71
Q

What is standard mortality ratio (smr)

A

Standard Mortality Ratio: The relative risk of death based on a comparison of an exposed to a non-exposed group. An SMR of 150 indicates the exposed group has a 50% greater risk of death compared to non exposed group

72
Q

What is relative risk (rr)

A

Relative Risk: Similar concept as SMR but looking at risk of disease rather than risk of death. Ex. RR=175 means a 75% increase in risk.

73
Q

Describe epidemiological studies - specificss

A

measure the risk of illness or death in an exposed population compared to that risk in an identical unexposed control population (ex. same age, sex, race, geographical area, environmental and lifestyle influences, etc.)

74
Q

What could go wrong in study

A

Bias, confounding chance

75
Q

What is selection bias

A

Study group is not representative of pop it came from
Groups not comparable

76
Q

What is information bias

A

Subjects are misclassified as to disease or exposure status
Recall bias = when ppl asked to remember
Info not accurate

77
Q

What are confounding factors

A

Study and control pops diffe with respect to factors which might influence occurrence of disasters
Smoking = confounding factor
Designed wrong, forgot to ask

78
Q

Describe health risk assessment

A

Process by which potential adverse health effects of human exposure to etiological agents (usually chemicals) characterizes

79
Q

How are risks characterizes

A

Hazard identification —> dose response assement
Exposure assement - how much pop exposed
For gov and municipalities to decide what is safe for pop

80
Q

Describe hazard identification

A

What adverse effects does agent casue if any
Toxicology studies
Biological medical and physical science studies,
Risk mangamnt - gov decides

81
Q

Describe what govs do

A

Once risk characterized = decide risk management
Cost vs risk
Ex = bisphenol a in baby bottles, bc babies vulnerable, potential endocrine disrupt or

82
Q

Describe lead

A

Bad for adults, especially children
Recap toys, kids put toys in mouth, many toys from diff countries

83
Q

What can lead affect

A

Hearing, growth, intellectual dev
Affects at low concentrations in kids

84
Q

Where lead found

A

Not biodegradable
Remains in envrieomtn
Lead pipes - lead in water
Peeling lead paint,soil, crystal, cans

85
Q

What effects of lead

A

Cns effects, gi effects, gets worse with time
No safe exposure level in children = impaired intellectual function at lower levels
Negative effects on child iq when exposed to lead

86
Q

What does lead alter

A

Alters function of divalent cations, many ca affecting ion channels, many proteins
Leads to loos excitatory glutamate receptors
Enters cells, many functions

87
Q

Describe toxicokinetics of lead

A

Goes everywhere in body
Stay in body or bone
Lead accumulates in bone
In bone = leaches our at diff times
Dangerous for bald eagles, water birds (water—> fish —> birds)

88
Q

Describe mercury

A

Released from volcanoes and varies industries (anthropogenic)
Gets into atmosphere, runoff land into warer
Mercury becomes methylated = bioaccumulates, not biodegradable, biomagnifies

89
Q

Describe effects of mercury on body

A

Short term = cns, memory loss, impaired hearing vision speech, peripheral difficulties
Dteterotiation of nervous system

90
Q

Describe grasshopper effect

A

Global distillation
Air rises in hotte regions of planet
When seasons change = air masses move north, temp cools down and contaminants washed down onto ground and seltzer
Mercury hops north each season
Persistent organic pollutants
Bioaccumulates = algae —> shrimp —> aortic cod —> seal —> polar bear

91
Q

Describe pesticides

A

Needed in some circumastanes
Deals with harvest losses due to weeds, disease, insects

92
Q

What do insecticides target

A

Nervous system of insect and person
can act pre and post syntactically

93
Q

How are insecticides useful

A

Decreased >30 human diseases
Malaria, yellow fever, plague, African sleeping sickness
Mosquitoes, ticks, lice fleas

94
Q

Describe oral ld50 in species - variation

A

Toxicity varies by species
DDT = rat 113, Trout 8
Parthion = rat 2, trout 2000 (v resistant )

95
Q

What are organochlorines

A

Chlorinated cipounds
DDT = used to kill insects, not safe for enrveioemnt, Saved 5 million lives, prevented 100million cases of disease through insect vectors

96
Q

What is ideal pesticide criteria

A

V low toxicity
Little or 0 persistence in environment
Little risk to non target organism = only effects isnect we want it to
Little development of resistance
Lipophilic chemicals accumulate in body dat of creatures exposed to it
Bioaccumulation of ddt>125 000 years - persistent
Enrveomtal half life v long = 10 years

97
Q

Why is ddt bad

A

Affected bird eggs
Bioacumulation

98
Q

How do organochlorides work

A

Act on voltage gated sodium channels
Nah channnel stays open longer
Insect structure more vulnerable than mammals

99
Q

What are pyrethroids

A

Insectidices
Similar mechanism of action

100
Q

Describe pyrethroids mechisn

A

Insect voltage gated na channel
Pyrethroids prolong opening = hyper excitability = convulse then die

101
Q

Describe organophosphate

A

Insecticide
Influence acetylcholinestherase

102
Q

What is malathion

A

Fam of organophosphate
Least toxic to mammals, have enzymes to rapidly metabolized

103
Q

Describe malathion mechanism of action

A

Death from excess stumaultion nicotinic receptor by ach
Organophosphate bound acetylcholineraste irreversibly
Paralyzed - death form resp failure

PHAR 300 (22 decks)

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