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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
Describe ricin more specifically
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
26
What are man made toxins
Toxins human release into environment Affect many systems Interfering with nervous system, calcium signalling, neuroendocrine, epignetic control
27
Describe what can be Lund in electronic waste
Neurotoxic mixtures Millions dumped into landfills = accumulate
28
What happens when computers discarded
Toxin leaches in to soil and water Volatilization = to air and now circulate
29
Describe substances most frequently involved in human poisoning
Drugs - accidental overdose Number of opioid deaths increasing Toxins at home Young children’s aged 1-3 = most vulnerable, until 5
30
Describe acute vs chronic toxicity
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
31
Describe air pollution
Can affect body Water, soil and air pollution
32
What is most voluenarble to pollution
Heart, lungs, brain
33
Describe air pollution
Breath in small particles all the time
34
Describe how far down in lungs diff types of particles go - >5um
Trapped in upper airways - bc mucus, muociliaey escalator traps particles - swallow and get rid
35
Describe how far down in lungs diff types of particles go - 1-5um
Smaller they get = the further they go Deep lung deposition
36
Describe how far down in lungs diff types of particles go - <1um
Reach pulmonary alveoli Through diffusion -through wall
37
Describe how far down in lungs diff types of particles go - 500nm
Phagocytoses by alveolar macrophages = can get rid but some can espace macrophages and go into blood
38
What can air pollution do to brain
Impaired dev - children Dementiah
39
How can air pollution get into brain
Lungs, swallow, absorb from gi, olfactory bulb
40
Describe diesel
Full of ultra fine particules —> emitted at high levels from exhaust of cars
41
Describe environmental cardiology
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
42
Describe Canada air
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
Describe micro particles
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
Describe cardiac organoid
Mixture of cells that have pacemaker activity = beat as same pace of heart Convenient and rapid
45
What do nanopartciles do
Reach circulation, cause atehrosclerosis
46
What is stenosis
Lumen = diameter decreased Severe before symptoms occur, will not know, wont feel it, can trigger blood clot
47
Describe air pollution - stats
>15 000 deaths/year from short and long term exposure 70% due to cardio and cerebreovascular disease
48
What can stenosis casue
Variable consequences, thrombus, embolus = occludes vessels, hemorrhage - if breaks due to wall damage from plaque Abnormal spams
49
What happen when occlusion in coronary artery
20% of people —> sudden death, heart goes into fibrillation
50
Describe stroke
Can have direct plug in brain Or clot forms in heart and can go to brain - pumped to brain
51
Describe enviroemtal toxicology
Things we exposed to in wate,r soil and air Try to make regulations
52
What does environment affect
Potential absorption Ex = humans sometimes will be exposed, sometimes wont be exposed
53
Describe bioavailability of toxin
Varies with location Ex= humans eat fish, fish eat shell fish with toxin, <—toxin in water
54
Describe biomagnification of ddt
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
What is ld50
Kill 50% of pop Botulinum toxin = 0.0001 - small amount v toxic
56
What do we want between ed50 and ld50
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
What do we want in toxicity dose response curve
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
What is NOAEL
HIGHEST data piny at which there was not an abserved toxic or adverse effect No observed adverse effect level
59
what is LOAEL
Lowest data point at which there was an observed toxic or adverse effect Lowest observed adverse effect level
60
What is hormesis
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
Describe animal testing
Largest proportion of animals killed = food Then roadkill V small portion for research purposes = strict regulations for animal tremanet in research
62
Is there regulations against animal cruelty in products sold
NOOOOO Glue traps = horrible MONTREAL RAT problem = warfarin used, will bleed internally = dies, painless tho
63
What is epidemiology
Conducted studies in humans to understand toxic ants in diff areas of world = to see what health problems they have
64
Describe observational studies
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
Describe Cohort studies
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
Describe cohort studies = types
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
Describe case control studies
Cases with disease Cases without disease Compare previous exposures Ask them questions - always retrospective Can find common issue
68
Describe cross sectional study
National census Computer will find links Begin with defined pop, gather data on exposure and disease
69
Summarize studies
Cohort = exposure —> outcome Case control = outcomes —> exposure Cross sectional study = exposures and outcome at same time
70
What is odds ration (o/r)
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
What is standard mortality ratio (smr)
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
What is relative risk (rr)
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
Describe epidemiological studies - specificss
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
What could go wrong in study
Bias, confounding chance
75
What is selection bias
Study group is not representative of pop it came from Groups not comparable
76
What is information bias
Subjects are misclassified as to disease or exposure status Recall bias = when ppl asked to remember Info not accurate
77
What are confounding factors
Study and control pops diffe with respect to factors which might influence occurrence of disasters Smoking = confounding factor Designed wrong, forgot to ask
78
Describe health risk assessment
Process by which potential adverse health effects of human exposure to etiological agents (usually chemicals) characterizes
79
How are risks characterizes
Hazard identification —> dose response assement Exposure assement - how much pop exposed For gov and municipalities to decide what is safe for pop
80
Describe hazard identification
What adverse effects does agent casue if any Toxicology studies Biological medical and physical science studies, Risk mangamnt - gov decides
81
Describe what govs do
Once risk characterized = decide risk management Cost vs risk Ex = bisphenol a in baby bottles, bc babies vulnerable, potential endocrine disrupt or
82
Describe lead
Bad for adults, especially children Recap toys, kids put toys in mouth, many toys from diff countries
83
What can lead affect
Hearing, growth, intellectual dev Affects at low concentrations in kids
84
Where lead found
Not biodegradable Remains in envrieomtn Lead pipes - lead in water Peeling lead paint,soil, crystal, cans
85
What effects of lead
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
What does lead alter
Alters function of divalent cations, many ca affecting ion channels, many proteins Leads to loos excitatory glutamate receptors Enters cells, many functions
87
Describe toxicokinetics of lead
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
Describe mercury
Released from volcanoes and varies industries (anthropogenic) Gets into atmosphere, runoff land into warer Mercury becomes methylated = bioaccumulates, not biodegradable, biomagnifies
89
Describe effects of mercury on body
Short term = cns, memory loss, impaired hearing vision speech, peripheral difficulties Dteterotiation of nervous system
90
Describe grasshopper effect
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
Describe pesticides
Needed in some circumastanes Deals with harvest losses due to weeds, disease, insects
92
What do insecticides target
Nervous system of insect and person can act pre and post syntactically
93
How are insecticides useful
Decreased >30 human diseases Malaria, yellow fever, plague, African sleeping sickness Mosquitoes, ticks, lice fleas
94
Describe oral ld50 in species - variation
Toxicity varies by species DDT = rat 113, Trout 8 Parthion = rat 2, trout 2000 (v resistant )
95
What are organochlorines
Chlorinated cipounds DDT = used to kill insects, not safe for enrveioemnt, Saved 5 million lives, prevented 100million cases of disease through insect vectors
96
What is ideal pesticide criteria
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
Why is ddt bad
Affected bird eggs Bioacumulation
98
How do organochlorides work
Act on voltage gated sodium channels Nah channnel stays open longer Insect structure more vulnerable than mammals
99
What are pyrethroids
Insectidices Similar mechanism of action
100
Describe pyrethroids mechisn
Insect voltage gated na channel Pyrethroids prolong opening = hyper excitability = convulse then die
101
Describe organophosphate
Insecticide Influence acetylcholinestherase
102
What is malathion
Fam of organophosphate Least toxic to mammals, have enzymes to rapidly metabolized
103
Describe malathion mechanism of action
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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