Transcript Toxicology - North Hills Preparatory

Toxicology
23 March 2015
Drug - a substance that when taken into the body
produces a physiological or psychological effects, usually
by interfering with the body’s normal chemical reactions
Poison – a substance that when taken into the body
produces death or physical harm, usually by interfering
with the body’s normal chemical reactions
Toxin – a naturally produced substance that when taken
into the body at very low doses causes death or physical
harm, usually by interfering with the body’s normal
chemical reactions
Drugs, Poisons, Toxins
Ricin – a by
product of
castor beans
How are they similar?
• Must be taken into the body (inhaled, swallowed, absorbed, or
injected) for effect
• Causes changes to the body by interfering with normal chemical
reactions
• All can be poisons in the right dose
How are they different?
• Drugs produce desired effects
• Toxins are naturally produced, and cause damage at very low
doses
Drugs, Poisons, Toxins
“All substances are poisons. There is
none which is not. The right dose
differentiates a poison and a remedy”
– Paracelsus 16th c. physician
Examples?
“All substances are poisons. There is
none which is not. The right dose
differentiates a poison and a remedy”
– Paracelsus 16th c. physician
Examples?
All drugs will become poisons at high doses.
● Tylenol, multivitamins, codeine, alcohol, etc.
“All substances are poisons. There is
none which is not. The right dose
differentiates a poison and a remedy”
– Paracelsus 16th c. physician
Examples?
All drugs will become poisons at high doses.
● Tylenol, multivitamins, codeine, alcohol, etc.
Moreover, things that are typically considered toxins are sometimes
therapeutic in the right dose.
● Arsenic is used to treat certain types of leukemia
● Botulin is used for botox, muscle spasms, crossed eyes, etc.
There are 5 main things which determine the toxicity
(adverse effects) of a poison:
1)
2)
3)
4)
5)
The chemical form of the substance
How it enters the body
The victim’s age, weight, gender, and condition
Time period of exposure
Presence of other chemicals
Determining Toxicity
There are 5 main things which
determine the toxicity (adverse effects)
of a poison:
1) The chemical form of the substance
2) How it enters the body
3) The victim’s age, weight, gender,
and condition
4) Time period of exposure
5) Presence of other chemicals
Example:
Arsenic, the metal, is not
absorbed by the body, and
so is not poisonous.
Arsenic compounds, such
as As2O3 and As2O5,
however, are readily
absorbed and very toxic.
Determining Toxicity
There are 5 main things which
determine the toxicity (adverse effects)
of a poison:
1) The chemical form of the substance
2) How it enters the body
3) The victim’s age, weight, gender,
and condition
4) Time period of exposure
5) Presence of other chemicals
Poisons can enter the
body through inhalation,
swallowing, absorption
through skin or mucus
membranes, or injection.
Determining Toxicity
There are 5 main things which
determine the toxicity (adverse effects)
of a poison:
1) The chemical form of the substance
2) How it enters the body
3) The victim’s age, weight, gender,
and condition
4) Time period of exposure
5) Presence of other chemicals
Fetuses, the very young,
the very old, and
individuals in poor
condition experience
greater toxicity.
The greater the body
weight, the less toxicity.
Women typically
experience greater toxicity
than men.
Determining Toxicity
Chronic exposure – toxin
There are 5 main things which
determine the toxicity (adverse effects)
of a poison:
exposure occurs over a long
period of time.
Acute toxicity – toxin
1) The chemical form of the substance
2) How it enters the body
3) The victim’s age, weight, gender,
and condition
4) Time period of exposure
5) Presence of other chemicals
exposure that is large enough
to cause immediate serious
problems
People with chronic exposure
build up some tolerance to the
poison, but will still
experience ill effects
Determining Toxicity
Synergist - drugs are
synergistic if their
There are 5 main things which
determine the toxicity (adverse effects) combined effects are
of a poison:
greater than the sum of
their individual effects (e.g.
1) The chemical form of the substance alcohol + some
antihistamines)
2) How it enters the body
3) The victim’s age, weight, gender,
Antagonists – drugs are
and condition
antagonistic if taking them
4) Time period of exposure
together reduces their
5) Presence of other chemicals
individual effects
Determining Toxicity
The toxicity of substances can be measured in animal trials.
• The poison is introduced to
test animals at different
dosages.
• The dose of poison that kills
half of the animals exposed
within a short time frame is
LD50 (50% leathal dose).
Measuring Toxicity
Which substance is
most toxic?
Why?
Botulin is most toxic
because it is deadly
in the smallest doses.
Measuring Toxicity
Which substance is
most toxic? Why?
Not an easy question!
Green has the lowest
LD50, and is the most
toxic at high doses.
Red is most toxic at
low doses.
Measuring Toxicity
Which substance is
most toxic? Why?
Not an easy question!
Green has the lowest
LD50, and is the most
toxic at high doses.
Red is most toxic at
low doses.
Doses where
red is most
toxic
Measuring Toxicity
Doses where
green is most
toxic
1. Determine the LD50 for each drug.
2. Compare the toxicity of the two drugs.
LD50 problem
Tylenol
LD50 rat = 3000 mg/kg
Recommended maximum daily dose for adults: 4000 mg
1) What dose would be fatal for 50% of rats, if an average rat
is 300g?
2) How much tylenol would a 150 lb person have to take to
equal the LD50 dose (calculated for rats)? (Hint 1 kg =
2.2lb)
3) How many tylenol capsules would a 150 lb person have
take to equal the LD50? (Hint 1 capsule = 500 mg)
Calculating Dose Levels
Tylenol
LD50 rat = 3000 mg/kg
Recommended maximum daily dose for adults: 4000 mg
1) What dose would be fatal for 50% of rats, if an average rat
is 300g? 90 mg
2) How much tylenol would a 150 lb person have to take to
equal the LD50 dose (calculated for rats)? (Hint 1 kg =
2.2lb) 20,000 mg
3) How many tylenol capsules would a 150 lb person have
take to equal the LD50? (Hint 1 capsule = 500 mg) 40
capsules
Calculating Dose Levels
Caffeine
LD50 rat = 192 mg/kg
1) What dose would be fatal for 50% of rats, if an average rat
is 325g?
2) How much caffeine would a 125 lb person have to take to
equal the LD50 dose (calculated for rats)? (Hint 1 kg =
2.2lb)
3) How many No-Doz capsules would a 125 lb person have
take to equal the LD50? (Hint 1 capsule = 100 mg)
Calculating Dose Levels
Caffeine
LD50 rat = 192 mg/kg
1) What dose would be fatal for 50% of rats, if an average rat
is 325g? 62.4 mg
2) How much caffeine would a 125 lb person have to take to
equal the LD50 dose (calculated for rats)? (Hint 1 kg =
2.2lb) 13100 mg
3) How many No-Doz capsules would a 125 lb person have
take to equal the LD50? (Hint 1 capsule = 100 mg) 131
capsules
Calculating Dose Levels
Although LD50 trials are still used today, their use has
declined over the last 20-30 years. Many people and
organizations criticize LD50 trials both for their cruelty and
their effectiveness.
Why might LD50 not be a useful measure of toxicity?
• Animal studies have limited relevance to humans
• We care about harmful effects, not just lethality
• The toxicity of a substance varies greatly according to all
the factors discussed before (age, gender, condition,
method, timing, other drugs, etc.)
Problems with LD50
1. Name 4 factors that affect the toxicity of a drug.
2. Estimate the LD50 of the drug shown below.
3. The LD50 of ricin is 0.02 mg / kg. What does that dose
correspond to in a 140 lb person? (1 kg = 2.2 lbs).
Exit Ticket
Toxicity Homework due next class
Bring materials to work on poisoner project next class – that
project will be due 3/27
Homework
What were our objectives, and what did we learn?
What was our learner profile trait and how did we demonstrate it?
How does what we did today tie to our unit question?
Closure