Transcript Toxicology
TOXICOLOGY Miss Colabelli What is Toxicology? • Study of how people and other living organisms interact with drugs and poisons What is Forensic Toxicology? • Use of toxicology and other disciplines such as analytical chemistry • Pharmacology and clinical chemistry to aid medical or legal investigation of death, poisoning, and drug use • Helps determine CAUSE and EFFECT relationships How a drug is broken down depends on… • Chemical properties of the drug • In the body • Age • Gender • Body impairment • Disease present • Tobacco/drug use • Exercise Metabolism • Drugs and poisons are metabolized in the liver by enzymes • The enzymes we each have is determined by our DNA (enzymes and proteins) • Enzymes vary person to person • Leads to personalized health care Half Life – T1/2 • Time it takes for the body to eliminate half of the drug present • Can be hours to days or weeks • Limits how long we can detect a drug or its metabolites Toxicity • Degree to which a substance is poisonous or can cause injury • Anything can be a poison in the right dosage • Too much water dilutes key components of blood leading to heart and kidney failure Dose • The amount of substance taken in by the body over a short period of time Acute Toxicity vs. Chronic Toxicity Acute Chronic Single dose Effects over long periods of time Effects seen in first 2-4 days May take years to become evident Doses typically higher than chronic Symptoms MAY be reversible Typically NOT reversible Research Acute and Chronic toxicity levels of Aspirin Acute Toxicity Chronic Toxicity Dosage Above 150mg per kg of body weight Below 100mg/kg taken over days or weeks Symptoms Nausea abdominal pain, organ failure Lethargy, dizziness, weakness and later liver and kidney damage Lethal Dose • Measure of the toxicity of a substance • LD50 – amount necessary to kill 50% of the population • Effect over entire population • Does not give probability of an individual dying • Some may have a greater sensitivity to a chemical • Refers to acute exposure Substance LD50 Water 90,000 Sugar 29,700 Table salt 3,000 Aspirin 1,750 Detergent 1,260 Ethanol 1,000 Morphine 500 Caffeine 200 Heroin 150 Lead 20 Cocaine 17.5 Cyanide 10 Nicotine 2 Batrachotoxin 0.002 Tetanus or botulina 0.000001 What is a drug? • Natural or synthetic • Compound used for physiological medical effects • Medicine • Chemical taken to help deal with generally accepted medical conditions • Drug • Implies chemicals taken for unintended or uncontrolled use U.S. Law • Drug • Substance intended for use in the diagnosis, cure, mitigation, treatment, or prevention of a disease or a substance intended for use as a component of medicine • Medicine • Substance used specifically in treating a disease Poisons, Toxins, Venoms • Poison • Compound designed with specific purpose of killing cells or organisms • Toxin • Subset of poisons • Produced by living organisms • Venom • Toxin injected directly into a victim Venomous vs. Poisonous • Venomous organisms use poisons for defense • Poisonous organisms unintentionally harm by ingestion, inhalation or skin contact Two types of Poisons Corrosive Metabolic Destroy tissue on direct contact Affect chemical functions of cells and tissues Act immediately Block biochemical pathways Strong acids and bases CO, Cyanide, heavy metals, Strychnine Compound Sulfuric Acid Hydrochloric acid Potassium Hydroxide Sodium Hydroxide Common Names Uses Vitriol, sour water Rain repellent (auto), laundry perfume/dye-free detergent, drain opener, car battery Muriatic acid, spirit or salt Toiler cleaner/disinfectant, rust and stain remover, laundry odor eliminator, tile cleaner, yard and garden muriatic acid cleaner, fish pond treatment Potash, caustic potash, potassium hydrate Batteries, automotive cleaner, tile sealer, household cleaning solution, oven/BBQ cleaner, drain opener, lawn “food”, non-aerosol hairspray, pesticides Ascarite, caustic soda, lye soda Batteries, car wash Drug & Poison Pathways • Absorption into bloodstream • Ingestion • Injection • Inhalation • Skin/mucus membrane • Distribution through circulatory system • Metabolism • Transformed into manageable waste primarily in the liver • Elimination • Urine, feces, skin, breathing out Drug Exposure • Intentionally • By treating illness or relieving pain • Accidentally • By harmful combinations or overdoses • Deliberately • By harming or killing others, or suicide Drugs of Abuse - Hallucinogens • Often derived from plants • Effect and intensity varies from person to person • Affects perception, thinking, self-awareness and emotions • Overdose • Increased heart rate • Increased blood pressure • Panic attacks, anxiety, or psychosis Drug Characteristics of Overdose MDMA (ecstasy) Increased heart rate and blood pressure, muscle cramps, panic attacks, seizures, loss of consciousness, stroke, kidney failure, death Mescaline Hallucinations, euphoria, dizziness, vomiting, increase heart rate, dilated pupils, diarrhea, headaches, anxiety, irrationality of thoughts LSD Dilated pupils, loss of appetite, sleeplessness, increase in body temperature, increased heart rate and blood pressure, sweating, dry mouth, tremors, confusion, distortion or reality, and hallucinations PCP Increased heart rate and blood pressure, convulsions, sweating, dizziness, numbness, and possibility of death from heart failure, drowsiness which can lead to accidents. Users sometimes exhibit psychosis (completely losing touch with reality) that can last for weeks Drugs of Abuse - Narcotics • Bring relief from pain • Puts person to sleep • Analgesics • Relieve pain by depressing nervous system • Most derived from Opium Drug Characteristics of Overdose Opium Difficulty breathing, low blood pressure, weakness, dizziness, confusion, loss of consciousness, coma, cold clammy skin, small pupils Heroin, Codeine, Morphine Difficulty breathing, low blood pressure, coma, spasms of the stomach or intestines, constipation, nausea, vomiting, sleepiness, blue fingernails and lips, death Methadone Difficulty breathing, drowsiness, coma, low blood pressure, muscle twitches, blue fingernails and lips Oxycodone Slow, difficult breathing, seizures, dizziness, weakness, loss of consciousness, coma, confusion, tiredness, cold clammy skin and small pupils Drugs of Abuse - Stimulants • Increases feelings of energy and alertness • Suppresses appetite • Depression often results afterwards • Tend to be highly addictive • Overdose • High blood pressure • Agitation • Confusion • Seizures Drug Characteristics of Overdose Amphetamines (speed) High blood pressure, rapid heart rate, agitation, irregular heartbeats, stroke seizures, coma, death Cocaine/crack cocaine Dangerous rise in body temperature, sweating tremors, seizures, irregular heartbeats, stoke, confusion, heart attack, bleeding in the brain, death Methamphetamines Dangerous rise in body temperature, profuse sweating, confusion, rapid breathing, increased heart rate, dilated pupils, high blood pressure, kidney failure, bleeding in the brain, death Drugs of Abuse – Anabolic Steroids • Chemical structure similar to testosterone • Promote cell and tissue growth increasing bone mass and body muscle Drugs of Abuse - Depressants • Affects nervous system by increasing GABA activity (neurotransmitter) • Increased GABA causes drowsiness, slowed brain activity • Relieves anxiety and produces sleep • Side effects: slurred speech, loss of coordination • Includes: • Tranquilizers, barbiturates, alcohol, valium/xanax Drugs of Abuse - Alcohol • Absorbed 20% by stomach and 80% small intestine • First effect – frontal lobe judgment • Concentration • Normal inhibition • Second effect with increased consumption is in the back of the brain • Language control • Motor skills • Body orientation • Vision BAC Tests • Field Sobriety • Horizontal gaze • Walk and turn • One leg stand • Breath Testing • Breathalyzer • Intoxilzer • Confirmatory Tests • Gas chromatograph-mass spectrometer Why is mercury poisoning also known as the Mad-Hatter’s disease? • Hat makers - used a mercury containing compound Bacterial Toxins • Tetanus • Produced by Clostridium tetani bacteria • Causes violent muscle spasms • Botulism • Produced by Clostridium botulinum bacteria • Paralyzes muscles • Causes irreversible damage to nerve ending • Extremely deadly in small amounts • Most poisonous biological substance Heavy Metals and Pesticides • Heavy metals • Ingestion, inhalation, through skin, mucous membranes • Poison • Pesticides • Control insects, weeds, fungi, etc • Toxic • Other lethal agents • Hydrogen cyanide (gas chambers) • Potassium chloride/sodium pentothal (lethal injections) Poison Characteristics of Overdose Pesticides (DDT, Aldrin, dieldrin) Interferes with the movement of nerve impulses and muscular contractions; anxiety, seizures, twitches, rapid heartbeat, muscle weakness, sweating, salivation, diarrhea, tearing coma, and death Lead Nausea, abdominal pain, insomnia, headache, weight loss, constipation, anemia, kidney problems, vomiting, blue coloration along gum line, seizure, coma, and death Mercury Acute poisoning from inhalation causes flu-like symptoms Poison Characteristics of overdose Arsenic Within 30 minutes of ingestion produces abdominal pain, severe nausea, vomiting, diarrhea, muscle cramps, convulsions, kidney failure, delirium, and death. Chronic exposure produces skin lesions, headache, personality changes, nausea, vomiting, diarrhea, convulsions, and coma Cyanide overdose can be fatal in 6-8 minutes after ingestion. Rapidly causes weakness, confusion, coma and pink skin from high blood oxygen saturation. Produces and almond-like odor. Strychnine enters the body by inhalation or absorption through eyes or mouth. Produces, within minutes, body spasms, temperature rises, violent convulsions, and death Practice of Forensic Toxicology • Test for presence and amount of a chemical in a forensic sample • Autopsy • Unidentified compounds • Chemicals extracted from evidence Questions that Forensic Toxicologists answer • What substance is in the sample? • What is the unambiguous ID of a chemical? • How much is present? • When was the compound taken? • Is the compound naturally occurring in the body, was it accidentally or intentionally put there? Tests • Physcico-chem methods • Titration, density, refractive index, etc • Spectroscopic • ID and quantifying based on absorption/emission • Chromatography/mass spectrometry • Separate mixture into it’s components; analysis of components • Immunoassay • Antibody-antigen specific reactions Types of Tests • Presumptive tests (Field) • Ex: Marquise reagent • Confirmatory Tests • Mass spectrometer • Immunoassay • Infrared spectrometer Samples • Fluid • Organs • Blood • Skin • Urine • Lungs • Vitreous humor • Hair • Oral fluid • Fingernails • Semen • Liver • Stomach contents • Kidney • Bile • Bone • Vomit • Heart • sweat • Brain Blood Samples • Blood near liver or organs tends to contain higher concentrations • Femoral artery • Urine Samples • Presence of drugs • Vitreous humor • Easily collected • Stable • Correlates with blood data