Toxicology23 March 2015

Drugs, Poisons, Toxins

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

Ricin – a by product of castor beans

Drugs, Poisons, Toxins

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

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.

“All substances are poisons. There is none which is not. The right dose

differentiates a poison and a remedy”

– Paracelsus 16th c. physician

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

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

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

Chronic exposure – toxin exposure occurs over a long period of time.

Acute toxicity – toxin 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

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

Synergist - drugs are synergistic if their combined effects are greater than the sum of their individual effects (e.g. alcohol + some antihistamines)

Antagonists – drugs are antagonistic if taking them together reduces their individual effects

Measuring 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 green is most toxic

Doses where red is most toxic

LD50 problem

1. Determine the LD50 for each drug.

2. Compare the toxicity of the two drugs.

Calculating Dose Levels

TylenolLD50 rat = 3000 mg/kgRecommended 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

TylenolLD50 rat = 3000 mg/kgRecommended 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

CaffeineLD50 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

CaffeineLD50 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

Problems with LD50

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.)

Exit Ticket

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).

Homework

Toxicity Homework due next class

Bring materials to work on poisoner project next class – that project will be due 3/27

Closure

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?