EXAM I010214Dosage makes response, determines whether substance is medicinal or poisonous. Could easily be either depending on levelShamans for knowing native plantsGenotyping is important in understanding effects of chemicals on individuals. Genes control reaction of chemicals in individuals and how they’re effected. Helps to determine who to use in clinical trials, because you would need everyone to react the same way.Framingham study: largest epidemiological study in Massachusetts using everyone in a population. Shows that plaque buildup can start as early as in teens.Clinicaltrials.govToxicity is usually a result of chemical structures with alkaloids (which contain nitrogen and are soluble in organic solvents). They have a bitter taste which helps to deter prey as a sort of evolutionarily adapted survival tactic. There is an increased level of alkaloid in younger leaves, because the plant hasn’t produced enough cellulose for animals to eat without killing the plant. Quantitative change in toxicity with maturation of plant.Ephedra plant (ma huang) is a stimulant that increases energy. Mixed with nicotine, it slows the breakdown of ephedra, putting the heart rate under stressContraindication: medicine + stimulant = bad reactionComplementary alternative medicinesCan only patent chemicals, not plants, which encourages extraction to make formulationsAnecdotal: by tradition, because others told you to… anything but prescribed by a doctor010314Vitamin E is a good antioxidantCotton in bottles to cushion pills and prevent them from breaking Garlic for heart disease. PlaceboSalem witch trials, women making bread from rye were absorbing chemical containing LSD through the skin. 010614ToxicologyPOWERPOINT 1Paracelsus: “the only difference between a medicine and a poison was the does.” All substances have a potential toxicity, even water. Body requires specific compounds, consuming excess of certain substances can deplete your body’s reserve. Poison ivy only poisonous to those who are susceptible- DOSE-RESPONSE RELATIONSHIPLethal does and LD50: -LD50: animals exposed to increasing doses of a substance. When 50% die, then it is lethal.-Expressed as mg of a chemical/kg of the body weight mg/kg-Could be oral, dermal, intravenous, or inhaled dose. -Expense of animals have become an issue, animal needs to be as pure as possible, all have same genetic background so they all respond the same way. Need to know exactly what the genetics are, need a large number of animals, need to be bred to be pure. (Used to use primates, not anymore)-Procedure: Determine chemical, perform LD50, look at liver of both the animals that die and thosethat survive. (Liver is the detoxifying organ, breaks down chemical which is either excreted or retained in liver)(Cirrhosis if overconsumption of alcohol). Must assume that the chemical isn’t flushed out immediately (alcohol stays in system) and that it goes to the liver. Analyze excrements daily, if nothing shows up, then you know it’s still in the body. Dosage given at a rate for which the animal can’t build a resistance.-Which has a higher LD50, a toxic chemical, or a very nontoxic chemical? Nontoxic requires a higher dosage to be toxic, so LD50 is highAcute toxicity: substance can do systemic damage after one time exposure to large dose and effects are almost immediately apparent. Can’t test clinically, because it occurs too easily.Chronic toxicity: damage caused by repeat exposure of bio-accumulation. Takes a long time to show symptoms in the bodyHigh blood pressure has to be induced for hypertonicDifference between acute and chronic depends on what part of the plant is being consumed- INDICATORS OF TOXIC RESPONSE-Death-changes in body temperature-pulse-respiratory rate-onset of nausea or vomiting-marker metabolites can also be present in tissues or fluids.-Nausea in an individual more than likely due to an alkaloid.-Measuring the amount of chemicals in the excrement is important because it tells you how much is being absorbed by the body.- HOW PLANT TOXINS DO DAMAGE1. Bind to receptors (phytohormones which is a hormone like compound derived in plants that alter synthesis patterns. Ex: soybean) (B-andrenoreceptors change blood pressure)2. Interrupt metabolism of carbohydrates, proteins, and lipids3. Affect specific organs (oxylates (like dumcane) and the kidneys, aconitite and the heart)4. Mimic neurotransmitters like serotonin - ABSORPTION AND ROUTE OF EXPOSURE-Inhaled through the lungs: mostly limited to allergic responses; sometimes inhaling essential oils. Ex: Agent Orange. The chemical itself is volatile. Darker skin would absorb the chemical.Changes enzymes in bloodstream, indicating the chemical has been absorbed. Chemicals inside of spores can be released through cell wall of spore and absorbed by alveoli, chemical is moved into the blood stream and can mimic neurotransmitters.-Skin: not often, but can be affected by suppositories and cosmetics. Mucus membranes acts like an internal skin. Shedding of mucus membranes-phlegm.-Oral ingestion: teas, tablets, capsules, tinctures (alcohol extract), raw herbsEx: DMSO byproduct of paper industry. Muscle relaxant for animals, but changed optics. Solubilizing agent. Metals present in the medium was being tied up by DMSO so body was not able to absorb them. Can also block absorption of toxins. Toxins require metals- EXCRETION-Main route: urine and kidneys-Lungs: rarer-GI tract: feces and urine-Sweat-Bile: secretion gets recycled -Ex: digitalis, first plant to be written up in a medical journal that was used for the treatment of heart disease. Still being used today. Diuretic, makes you pee by strengthening the heart muscle. However, it’s very toxic. With heart disease, you retain fluid.-Liver has detoxification enzymes- METABOLISMEnzymatic systems that are common to most animals-Induced: caffeine stimulates adrenaline (epinephrine) production and turns on MAO which breaks down neurotransmitters (decreased level) stimulated by the adrenaline-Inhibited: myristicin (from nutmeg) mildly inhibits MAO- neurotransmitters build up (increased level), and mild psychotropic intoxication occurs.- FACTORS AFFECTING POISONING -Solubility of toxin in biological medium. If relatively soluble, goes right through system.-Personal state of health: immune health, nutritional state, stress levels. More susceptible to toxins if individual has low protein.-Age: elderly and younger