CLINICAL TOXICOLOGY

• Toxicology


  The study of the adverse effects of a toxicant (xenobiotics) on living organisms
• Adverse effects (toxic effects)


  Any change from an organism's normal state, dependent upon the concentration of active compound at the target site for a sufficient time
• Toxicant (Poison)


  Any agent capable of producing a deleterious (harmful) response in a biological system
• Living organism


  Target sites, storage depots (adipose tissue, bone, liver, and kidney) and enzymes (respiration, digesting food, muscle and nerve function)
• Xenobiotic


  A substance or chemical that is foreign to a living organism's body, can be of natural or man-made origin (venom, drugs, pesticides, pollutants, industrial chemicals, etc.)
• Clinical Toxicology


  Focuses on the toxic effects of therapeutic and non-therapeutic agents including drugs of abuse, household products, pesticides, metals, radiation, and other chemicals in patients caused by accidental poisoning or intentional overdoses
• Poison


  Any substance which can cause injury, disease and death, when introduced into, or developed within the body, aka "corpus delecti" or "body of evidence"
• Toxicant


  Toxic substance produced by or a by-product of human made activities (e.g. dioxin and furans – not manufactured or produced intentionally but are created when other chemicals or products are made – during waste incineration, fuel burning – found in small amounts in air, water, & soil – highly toxic – carcinogenic)
• Toxin


  Toxic substance produced by natural sources (e.g. snake venom)
• Intoxication


  Toxicity associated with any chemical substance
• Poisoning


  Ability of a substance to cause injury, disease or death (overdose of drugs & biological products; wrong substance given or taken)
• Overdose


  Intentional exposure with the intent of causing self-injury or death
• Toxidrome


  A collection of signs, symptoms and laboratory findings that suggest a specific ingestion
• Risk


  The probability or likelihood that adverse effects will occur when a living organism is exposed to a toxin
• Hazard


  The likelihood that injury will occur in a given situation or setting
• Safety


  The probability that harm will not occur under specified conditions
• Toxicity


  Ability of a substance to cause biological change, leading to adverse effects
• Dose


  Actual amount of chemical that enters the body
• Selective toxicity


  That a chemical will produce injury to one kind of living matter without harming another form of life, although the two may exist close together
• Threshold level


  Dose or exposure level below which the harmful or adverse effects of a substance are not seen in a population
• No observed adverse effect level (NOAEL)


  The dose or exposure level below which no harmful or adverse effects are observed
• Individual susceptibility


  Differences in types of responses to hazardous substances, between people (1st (no effect), 2nd (seriously ill), 3rd (develop cancer))
• Sensitive sub-population


  Those persons who are more at risk from illness due to exposure to hazardous substances than the average, healthy individual
• Exposure limit


  The concentration of a substance to which most individuals may be exposed to repeatedly without adverse effects
• Household Plants


  • Talumpunay (Datura metel) – tropane alkaloid (atropine, hyoscyamine & scopolamine)
  • Dieffenbachia plant - calcium oxalate (intense discomfort – pain and edema)
  • Rosary pea (Abrus precatorius) – abrin – preventing cells from making proteins the body needs
  • Tangan-tangan/Castor bean (Ricinus communis) – ricin (cause respiratory distress – difficulty of breathing)
  • Tropane alkaloids – at high dose could result in delirium and intense hallucinations
  • English yew (Taxus baccata) – taxine (nausea, vomiting, dizziness, abdominal pain, tachycardia, muscle weakness and confusion)
  • Deadly nightshade (Atropa belladonna) – atropine, hyoscyamine and scopolamine
  • Angel's trumpet (Brugmansia suaveolens) (all parts contains tropane alkaloids)
  • Suicide tree (Cerbera odollam) – cerberin (nausea, vomiting, hyperkalemia, & thrombocytopenia – low number of thrombocytes which can result in bleeding problems
• Information Resources


  • COMPUTERIZED DATABASES - POISINDEX (primary resource for poison control centers)
  • PRINTED PUBLICATIONS - Medical Toxicology: Diagnosis & Treatment of Human Poisonings, Drug-Induced Ocular Side Effects, Clinical Ocular Toxicology, Goldfrank's Toxicologic Emergencies, Toxicology of the Eye, Clinical Management of Poisoning and Drug Overdose, Poisoning and Drug Overdose
  • INTERNET - Center for Disease Control and Prevention, U.S. Food and Drug Administration, National Library of Medicine, National Institute for Occupational Safety and Health, American Society of Health-System Pharmacists, Material Safety Data Sheets, U.S. Environmental Protection Agency
  • POISON CONTROL CENTERS - provide information to the general public and health care providers, most reliable and up-to-date sources of information
• PAPYRUS EBERS contained information pertaining to many recognized poisons - hemlock, aconite, opium and metals (lead, copper and antimony)
• The Book of Job (Job 6:4) speaks about poison arrows
• Strychnos toxifera added a number of poisons and clinical toxicology principles pertaining to bioavailability in therapy and overdosage
• Aposematic signals are primarily visual, using bright colors and high contrast patterns such as stripes
• Larger doses (400 mg) of caffeine can cause headache, anxiety and chest pain, irregular heartbeat and death
• For healthy adults, FDA cited 400 mg per day (about 4 or 5 cups of coffee) associated with dangerous negative effects
• Theophrastus, the Father of Botany and student of Aristotle, included numerous poisonous plants in his writings
• Dioscorides classified poisons into plant, animal, and mineral poisons in his book De Materia Medica (contains reference to 600 plants)
• Hippocrates compiled a listing of a number of poisons and outlines some clinical toxicology principles, noting the effect of foods, occupation and climate in causing diseases
• Maimonides (Moses ben Maimon) wrote a treatise on the treatment of poisonings (insects, snakes & mad dogs), subject of bioavailability, noting that milk, butter, and cream could delay intestinal absorption, and stated "No disease that can be treated by diet, should be treated with any other means"
• Percival Pott found that soot caused scrotal cancer in chimney sweeps, and the carcinogens found in soot were polycyclic aromatic hydrocarbons (PAHs) which are slightly mutagenic, but their metabolites can be potent mutagens that damage chromosomes and play an important role in carcinogenesis
• Catherine de Medici tested toxic concoctions, carefully noting the rapidity of the toxic response (onset of action), the effectiveness of the compound (potency), and the degree of response of the parts of the body (site of action) and the complaints of the victim (clinical signs and symptoms)
• Paracelsus, the Father of Modern Toxicology, developed the concept of "dose" and stated "All substances are poisons; there is none that is not a poison. The right dose differentiates a poison from remedy"
• The WHO bases its acute hazard rankings on the rat oral LD50, the lethal dose (mg/kg BW) that kills 50% of the test animals, using the Globally Harmonized System of Classification and Labelling of Chemicals