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104 Cards in this Set
- Front
- Back
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What is the smallest we can analyze substances?
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parts per trillion (PPT)
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What is Three Tree Poison?
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In 1595 in South America it was used to hunt monkeys as it increases in potency its thre tree, two ree and one tree dead refers to the curare plant
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What was in Three Tree Poison?
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Curare
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What did Claude Bernard find in 1844?
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discovered that curare blocked nerve impulses that contected the central nervous system to muscles
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What does the central nervous system consist of?
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the brain and the spinal cord
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What is the active ingredientin curare?
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tubocuranine
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Who was Dr. Harold Griffith?
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The first physician to use curare to relax the muscles of a patient undergoing an appendectomy which took plae in Queen Elizabeth Hospital in Montreal
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What is Pancuronium Bromide?
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an engineered version of curare could be lethal it overdose
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What are the lethal injection chemicals?
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Sodium Thipentol: induces sleep Pavulon: attests breathing Potassium Chloride: stops the heart
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Is curare a poison or a drug?
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both
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What preceded penicillin as an antibiotic and what was it sed for?
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Sulfanilamide and was used to treat gonorrhea and strep throat. First mixed with a bad elixer: diethelyne glycol and Watkins is blamed 1937
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What is an elixir?
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drug dissolved in alcohol
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Who was Harold Watkins?
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company chemist that used diethylene glycol as the sovent for sulfanilamide to make it sweeter and easier to swallow but didn't know it causes kidney and liver failure causes abdominal pain, vomiting, blindness and death. Got blamed for the 100 deaths and committed suicide
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What happens to Diethylene Glycol when it enters the body?
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Is converted to Oxalic Acid which is toxic to the liver and kidney
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Who was Frances Kelsey?
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Woman who found connection between deaths and diethylene glycol. Received Medal of Honor for work on Thalidomide which caused birth defects
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Due to the extreme failure of the elixir sulfanilamide what happened?
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President Roosevelt signed the 1938 Food Drug and Cosmetic Act
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Who was paracelsus (1493-1541)?
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Was the father of modern toxicology. Recognized substances could be used to treat ailments and dosage very important. Used Mercury Sulfide to treat syphilis
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Is there a threshold effect to dosage?
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yes below which no averse effcts
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What is Hormesis?
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investigation of substances at very low doses because they may behave differentlly at higher doses
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Is it possible that at small doses there are beneficial effects but below that causes adverse effects?
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yes
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Is Vitamin D toxic?
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at high doses yes at small doses beneficial
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Can a few molecules be more potent thant many more molecules?
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yes a target of the drug may be affected to the presence of very few of the active drug while a saturation of that drug would not produce the same response
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What toxin do lima beans and apples contain?
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cyanide but lethal dose is 10,000 mg
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What does the puffer fish contain and what is the lethal dosage?
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tetrodotoxin 10 mg
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What causes Botulism poisoning? Where was it first found?
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By Clostridium botulinum bacteria first found in sausages also found in garlic. Grows and multiplies in conditions where there is a low oxygen supply. Lethal dose is .03 mg
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What is added to processed meats to prevent bacterial growth?
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nitrites
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What is Botulin toxin used for in medicine?
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to prevent tremors, botox, ease migraine pain and chronic anal fissures
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Does the type of exposure matter in toxicology?
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YES! inhalation vs ingeston or exposure through the skin
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What is biochemial individuality?
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the difference in toxicological responses in different individuals upon exposure to the same substance
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What is the teratogenic effect?
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it affects the offspring. Mother unaffected but kids will be
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What is epidemiology?
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used to try to understand the toxicity of substance in past human cases
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What is the Nocebo effect?
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people who are told that a particular substance is dangerous will react negatively to it regadless of the real nature of it
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Is Aspartame bad for you?
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NO
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When did we start studying the safety of the materials we are exposed to?
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1903
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Who was Dr Harvey W Wiley?
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The chef of the bureau of chemistry. Forerunner of the FDA. Looked at substances put into the food supply to determine if were hazardous
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Who where the "Poison Squad" of 1903?
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12 volunteers who ate food prepared by Chef Carter who added something different to eery meal. Each additive was a substance that was normally usd in the gneral food supply. Voluntteers given dosages rangin from .5 to 4 grams. The food was weighed and feces and urine of individuals were collected. Symptoms were: Nausea, vomiting and stomach aches
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What did Wiley convince the govt of?
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The Pure Food and Drug Act of 1906
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What is detoxification?
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largely an enzymatic process. Enzymes get rid of foreign invaders (toxins).
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What do Phase 1 Enzymes do?
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Increase solubility of a toxic substance if it is not soluble provides a site of attachment on that molecule for phase 2 enzyme. It alters the molecular structure
ex of phase 1 cytochrome P450 |
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What do the Phase 2 Enzymes do?
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Attach to the modified compound and eliminates it from the body
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What are Benzopryenes?
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compounds that form during barbequing. Found in meat.
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What are Benzopryenes composed of?
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multiple aromatic rings, not very water soluable
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When there is an oxygen atom in the structure of a molecule what does that mean?
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hydrogen bonds may form between the molecule and water so it will be water soluble
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What does the phase 1 enzyme add to the molecule?
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an oxygen
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When the altered moleucle interacts with DNA what happens?
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it causes a mutation which can lead to cancer
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Can the body be tricked into making detoxification enzymes?
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yes ex is tea which contains compounds that the body perceives to be dangerous. The extra detoxification enzymes produced in response to tea may eliminate other foreign substances so is called anti-carcinogen
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Why are Broccoli and Brocco Sprouts good for s?
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The body perceives the compounds in them to be toxic so it generates enzymes to get rid of sulforaphane (compound)
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What is St John's Wort?
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A mild anti-depressant
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Can drugs not be metabolized and eliminated due to cytochrome P-450 (Phase 1 enzyme)
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yes. Tetracycline, Contraceptives, Protease Inhibitors, Antidepressants, Xanax, etc
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What is the benefit of Acetaminophen over Aspirin?
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does not cause gastric bleeding and is not a blood thinner
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Can Acetaminophen cause liver damage?
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yes. detoxification process can lead to liver damage to Clucuronyl Transferase (Phase 2 Enzyme) attaches to a Clucuronic Acid molecule
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Is Acetaminophen soluble?
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yes why doesn't need phase 1 enzymes
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What is Glucuronyl Transferase?
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a Phase 2 Enzyme
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What can an overdose of acetaminophen lead to?
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There may not be enough glucuronic acid in the bloodstream to eliminate all of the drug so a different enzyme enters to remove the excess drug: Cytochrome P-450 which changes structure of moleucule and converts it to N-acetyl-p-benzoquinone imine which is very reactive intermediate which DAMAGES LIVER. Then the second backup system uses Glutathione-S-Transferase (Phase 2 enzyme) to remove new harful intermediate by attaching a glutathione molecule to it but if not enough glutathione available it can't be disposed of
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What is Cytochrome P-450?
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A phase 2 enzyme that can change the structure of acetaminophen
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What is Glutathione-S-Transferase?
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The phase 2 enzyme in the second backup system that tries to get rid of altered acetaminophen structure
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How do you make sure enough Glutathione is in the blood?
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It is synthesized from teh conversion of the Methionine amino acid. The acetaminophen tablet should (but doesn't) include a certain portion of methionine to ensure there there is a limited effect on the liver
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What does alcohol stimulate?
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Cytochrome P-450 activity so stimulates the formation of the reactive intermediate that is harmful to our livers (it is what changes the structure)
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Why will it not work to consume glutathione in pill form?
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it is a tri-peptide so composed of three amino acids and is subjected to degradation down to the individual amino acid level once it hits the stomach so never makes it to the bloodstream
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What does Glutathione synthesis require?
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the amino acid Cysteine
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What does cysteine need to be released into the bloodstream?
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N-Acetylcysteine
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What can you take with acetaminophen to reduce the possibility of liver damage?
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N-Acetylcysteine. What hospitals give when patient overdosed on acetaminophen or has been drinking during its consumption
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What proteins are high in cysteine?
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high cysteine whey protein
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Why are individuals with a high-carbohydrate intake diet less likely to suffer from acetaminophen overdose?
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Carbohydrates broken down to yield glucose which is required to make glucuronic acid which is needed by the enzyme that detoxifies acetaminophen
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How do red blood cells help in detoxification?
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Theytrasport oxygen with the hemoglobin (which is heme which binds with the oxygen and protein) once hemoglobin performed function eliminated through urine. Heme broken down to yield biliverdin which converts to BILIRUBIN which is excreted (glucuronic acid attaches to Bilirubin to make it more soluble)
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What is Jaundice?
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Insufficient Glucuronyl Transferase
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What causes the yellow discoloration?
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The accumulation of bilirubin under the sin which also accumulates in the brain and can cause death
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What are used to prevent jaundice in babies?
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Blue "Bili" lights because effectively change the of the bilirubin molecule to make it more soluble
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What is seldane?
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a drug used to relieve hay fever and allergies and was first non-sedating anti-histamine. When it is ingestd it is foreign so phase 1 enzyme converts it to a more soluble form which makes it the active form (when first ingested it is not active)
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What is the metabolically active form of Seldane with no risk of heart attacks?
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Allegra
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What are the purpose of antihypertensives?
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they aim at reducing blood pressure
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What is Felodipine?
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a common antihypertensive drug is metabolized by Cytochrome P-450
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What effect does grapefruit juice have on Felodipine?
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It inhibits the formation of Cytochrome P-450 and so the drug is not being broken down as much so the levels of the drug will be higher so it will lover a patien's blood pressure too much why don't serve grapefruit juice at hospitals
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What are Furanocoumarins and what can they be used for?
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they are the compounds found in grapefruit jucie that are responsible for inhibiting the Cytochrome P-450. They could be used by adding them to the the antihypertensives to reduce the amount of dosage that has to be put into the drug
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What is erthromycin?
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an antibiotic which is also metabolized by cytochrome enzymes. has ability to induce irregular heartbeats if levels of the drug rise about normal
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What are monoaminexoxidase Inhibitors (MAOIs)?
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they are inhibitor Monoamine oxidase which break down naturally occurring chemicals such as norepinephrine, serotonin and dopamine which are responsible for setting our moods
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Why do individuals suffer from depression?
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the chemicals responsible for setting our mood are broken down fater. MAOIs inhibit the breakdown of these chemicals so depression less likely to occur
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What interfere with the activity of MAOIs
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aged cheese, red wine and salami
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What do the goods that inhibit MAOIs contain and what does it do?
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They contain Tyramine which increases blood pressure. It is broken down by MAO
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What happens if you are consuming large amounts of tyramine while doing a MAOI treatment?
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it can lead to very high blood pressure (hypertension) because the tyramine is not being broken down so can lead to stroke
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What is the most toxic man-made chemical?
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dioxin
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What are two features that all dioxins share?
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a central structure with oxygens and chlorine
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What is a term that is interchangeable with dioxin?
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TCDD
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How many chlorines are needed for the toxicity of TCDD?
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4
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Who began the history of dioxins?
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Charles Darwin realized that plants are governed by chemicals known as Plant Hormones
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What was Auxin?
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The first plant hormone to be extracted important because brought to mind possible of treating plants with hormones and also was used as a week killer
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What are the two chemicals that were invented to mimic the properties of Auxin and have similar structes?
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2-4-D and 2,4,5-T
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What are the origional herbicides?
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2-4-D and 2,4,5-T
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What is Chloracne?
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mixture of 2,4-D and 2,4,5-T which would create pimples
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What is Agent Orange?
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mixture of 2,4-D and 2,4,5-T
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What was Operation Ranch Hand?
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Sprayed Agent orange to defoliate trees so they couldn't hide under trees
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What did they find in 1969 regarding 2,4,5-T
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they caused birth defects due to TCDD contamination
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What is the most potent carcinogen ever tested on animals?
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TCDD
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Why didn't the levels of TCDD in the environment not drop after they stopped manufacturing 2,4,5-T?
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because TCDD is a byproduct of other industrial processes such as bleaching pulp to make paper (compounds in the wood react with chlorine) also white paper coffee filters and certain plastics
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What is the element that is crucial to form TCDD?
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chlorine
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Is it not safe to heat up plastic in the microwave?
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no its completely safe because that plastic doesn't contain chlorine
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What happened in Seveso and when?
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In 1976 a chemical plant inadvertently released large amounts of Dioxins and citizens were exposed so after cleaned they were studied
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What was the result of the Seveso studies?
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Men exposed seemed to have more female babies
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How does a cacinogen work?
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it can travel across cell membranes, bind to a receptor, and disrupt DNA causing mutations
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What famous political figure was "poisoned" with dioxin?
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Viktor Yuschenko the president of Ukraine. Only thing that happened was the Chloracne
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Since 2,4,5-T only has 3 chlorines how do you produce Dioxin?
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join two 2,4,5-T molecules
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What is the difference in structure between 2,4-D and 2,4,5-T?
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The 2,4-D doesn't have a chlorine on the left so when two 2,4-D molecules react they form a harmless Dioxin that only has 2 chlorines instead of 4
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Is the conclusion that lawn chemicals cause cancer valid?
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no
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What is Love Canal?
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A community near Niagra falls that was shut down due to a chemical company dumping chemicals including Dioxins near the town People didn't want ot stay in town because of smell of chemicals and fed govt moved scared population out of the town it was hard to sell their houses but no diseases actually linked
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