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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