Toxi lec m2pt2

• TOXICOKINETICS


  The study of the kinetics of poison throughout the body “What the body does to the poison?”
• TOXICOKINETICS


  Modeling and mathematical description of the time course of disposition of toxicants in the whole organism.
• TOXICOKINETICS

  Important principle

  The effect which a chemical produces is not only dependent on the dose administered but more on the concentration of the chemical in the target organ. The concentration in turn depends on the disposition of the chemical.

  The kinetics of a chemical/drug may differ from therapeutic dose to its toxic dose.

  The study of toxicokinetics is important in predicting plasma concentration of a chemical
• TOXICOKINETICS


  It is the study of the drug movement around the body.

  It determines the no. molecules that can reach the receptors or site of action.
• dose


  All chemicals and biological systems follow a dose-relationship
• dose


  It determines whether a chemical is beneficial or poisonous
• toxic response


  Proportional to the concentration of the chemical at the target site
• Dose-response


  Relationship between exposure and health effects can be established by measuring the response relative to an increase in dose
• Dose-response


  Important in determining the toxicity of a particular substance
• Toxic effects


  -Health effect that occur due to exposure to a toxic substance
• Local (Chemically active/irritant toxicants)


  Possess pronounced physiochemical properties
• Local (Chemically active/irritant toxicants)


  Affect skin, lungs, nasal cavity, eyes

  • Ex: Phosgene, Mustard gas, Chlorine
• Systemic


  Target organ toxicity
• Systemic


  Result of accumulation
• Systemic


  Affects highly perfused organ

  • Ex: Heavy metal poisoning that accumulates in liver and kidneys
• What is the beneficial dose of ASA?

  300 - 1000 mg
• What is the toxic dose of ASA?

  1000 mg to 3000 mg
• What is the beneficial units/day of Vitamin A

  5000 units/day
• What is the toxic units/day of Vitamin A?

  50000 units/day
• What is the beneficial % of oxygen?

  20 %
• What is the toxic % of oxygen?

  50 - 80 %
• Vitamin A has therapeutic and toxic effects

  > TOO LOW: Blindness, dry skin, and increased infection

  >TOO HIGH: Anorexia anemia nose bleed, muscle and joint pain
• Threshold


  Dose/exposure level below which the harmful and adverse effect of a substance are not seen in a population
• Threshold


  Also referred to as the “No observed adverse effect level or No effect level”
• LD50


  Smallest dose that kills 50% of the population, all routes except inhalation and aquatic exposure
• LC50


  Smallest dose that kills 50% of the population, use for inhalation and aquatic exposure
• TLV


  max amount of drug considered to be safe
• ED50


  dose that exhibits desired effect in 50% of population
• TLV

  Threshold Limit Value
• Therapeutic Index


  measure of safety, ratio of LD50 to ED50
• Absorption


  is the process by which a chemical enters the body
• Distribution


  is the stage when a substance moves from the site of entry to other organs/areas of the body
• Metabolism


  is when the body transforms the chemical into metabolites
• Excretion


  is the process wherein the parent chemical and its metabolites leave the body
• • Highly perfused Organ and Poorly perfused

  • Most toxins are H2O soluble

  • Rate limiting step for Distribution is Blood Flow.

  • High excretion means LOW risk of toxicity
• Duration and concentration at the portal of entry


  The higher the concentration, the greater will the damage be
• Rate and amount of chemical absorbed


  rate of absorption is slow and the amount absorbed is small, the toxicity will be low
• Distribution of the toxicant within the body

  • most of the toxicants are distributed in highly perfused organs which have vital functions such as the brain and the kidneys.
  • the organ in which a chemical is most highly concentrated is not necessarily the organ where most tissue damage occurs.
• Efficiency of biotransformation and nature of metabolites

  a chemical maybe converted to a toxic metabolite which is more toxic than the parent compound
• The ability of the chemical or its metabolites to pass through cell membranes and come into contact with specific cell components

  A chemical can pass through the placenta or the blood brain barrier