EXAM I 010214 Dosage makes response determines whether substance is medicinal or poisonous Could easily be either depending on level Shamans for knowing native plants Genotyping 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 gov Toxicity is usually a result of chemical structures with alkaloids which contain nitrogen 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 stress Contraindication medicine stimulant bad reaction Complementary alternative medicines Can only patent chemicals not plants which encourages extraction to make formulations Anecdotal by tradition because others told you to anything but prescribed by a doctor and are soluble in 010314 Vitamin E is a good antioxidant Cotton in bottles to cushion pills and prevent them from breaking Garlic for heart disease Placebo Salem witch trials women making bread from rye were absorbing chemical containing LSD through the skin 010614 Toxicology POWERPOINT 1 Paracelsus 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 RELATIONSHIP Lethal 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 those that 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 high Acute 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 body High blood pressure has to be induced for hypertonic Difference 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 DAMAGE 1 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 lipids 3 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 herbs Ex 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 METABOLISM Enzymatic 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 enzymatic metabolism not fully formed Genetics is it an adaptation Allergies overtime body changes in its response Higher effect on younger ADDITIONAL CONCERNS Contaminants mycotoxins naturally occurring