AP0418 - toxicology

• Toxicology


  The study of poisons and their effects particularly on living systems
• Toxicology is a broad field, overlapping with biochemistry, histology, pharmacology, pathology, and many other disciplines
• Toxicology also overlaps with forensic science and environmental science
• LD50


  Lethal Dose that kills 50% of the population
• TD50


  Toxic Dose that affects 50% of the population but the definition of what toxic means has to be defined
• Dosage is normally measured in mass of toxin per body mass
• ED50


  Effective Dose that produces the desired effect in 50% of the population
• Therapeutic index


  LD50/ED50 (or TD50/ED50 for therapeutic drugs)
• Dose-response curve


  • Characterizes the response to different levels of a drug or toxin
  • Ideally the effective dose and the toxic dose are well separated
  • Each individual will have their type of response which changes across a dose range
• Clark's rule


  A vintage way to calculate a child's dose based on their mass: Child's dose = (mass of child in kg x adult dose)/70kg
• Factors affecting dose-response curve

  • Tolerance (metabolic or behavioural)
  • Food in the stomach
  • Biological variability (age, Circadian rhythm, obesity)
  • Genetic differences between individuals
• Drug interactions


  Drugs may potentiate each others effects (synergism) or nullify the effects of one or both
• Biological poisons


  • Foxglove (Digitalis pupurea)
  • Deadly nightshade (Atropa belladonna)
  • Death cap (Amanita phalloides)
  • Black widow (Lactrodectus mactans)
  • Scorpions
• Ricin


  A poison that can be made from the waste products of castor bean processing, affects a cell's ability to produce protein, 0.02-0.03g per kg toxicity, no antidote exists
• Chemical xenobiotics


  • Household: detergents, acids, paints, paint thinners, cosmetics, gardening treatments
  • Industrial: sheep dip, organophosphates, industrial solvents
  • Gases: hydrogen cyanide, carbon monoxide
  • OTC/Prescription: paracetamol, diazepam, codeine
  • Drugs of abuse: alcohol, pharmaceutical preparations, illegally manufactured synthetic active drug substances
• Carbon monoxide


  Colourless, odourless gas, product of incomplete combustion, replaces oxygen attached to Hb, treatment is administration of oxygen, recovery may involve mental confusion, severe headaches, cardiac problems and CNS problems
• ADME


  1. Absorption

  2. Distribution

  3. Metabolism

  4. Elimination
• Metabolism (or biotransformation)


  1. Phase I: functionalisation reactions

  2. Phase II: conjugation reactions
• Phase I reactions are intended to deactivate (detoxify) molecules, but sometimes they do the opposite (e.g. produce active metabolites, which in some cases can be more potent than the drug itself)
• Phase II reactions produce water soluble metabolites which can be easily excreted from the body (though the kidneys into urine)
• The kidney is the most important organ for elimination of xenobiotics and /or their metabolites