Toxicology Test 1

  1. Poison
    Any agent that is capable of producing injury or death when ingested or absorbed
  2. Toxicology
    • Basic science of poisons
    • science of adverse effects of chemicals on living organisms
  3. toxicologist
    public health relevance of chemicals and chemical exposure
  4. All drugs are chemicals but.....
    not all chemicals are drugs
  5. Mechanistic toxicology
    binding at molecular level
  6. regulatory toxicology
    • policy issues with chemical exposure
    • FDA
  7. Descriptive toxicology
    • examining what damage a poison can produce
    • ex. acetaminophen decreases glutathione and cause liver damage
  8. specialized toxicology
    • clinical: drug-drug, overdose, underdose
    • Forensice: medical legal aspects of poison
    • investigative
  9. Orgins of toxicology
    • physics: 1st order, 0 order
    • biochem: feedback mech, molecular level
    • medicine: treatment
    • biology: algae growth, life outside body
    • physiology: fxn of organ systems
    • (pharmacology)
  10. Are all substances poisons?
    • yes depending on the dose or concentration
    • timing also included in case of newborn (biological system can handle substance)
  11. Delaney clause (1958)
    make sure all drugs on the market are safe and efficacious
  12. thalidomide incident
    gave FDA their power, gave to pregnant women for nausea and it caused major birth defects (no arms)
  13. Modern toxicology incidences
    • delaney clause (1958)
    • thalidomide incident
    • diethylstilbestrol (DES)
    • rachel carson's silent spring
  14. What is the cheif organ in toxicology?
    The liver is the largest organ because of presence of poison in nature (we are exposed all the time.
  15. Diethylstilbestrol (DES)
    used to prevent abortion or miscarriage or premature labor, caused major problems. (origionally recommended in all pregnancies)
  16. Silent springs by rachel carson
    • Wrote a book about the effects of pesticides on environment...DDT wiping out condor, egg shells soft
    • DDT: man made and accumulates in naure.
  17. Spectrum of undesired events
    • Allergic rxn
    • idiosyncratic reactions
    • immediate vs. delayed toxicity
    • reversible vs. irreversible toxic effects
    • local vx systemic toxicity
    • interaction of chemicals
    • tolerance
  18. Allergic reactions
    • hypersensitivity, illicit immune system response vs. local
    • previous sensitivity
    • can happen with really low doses
  19. Idiosyncratic rxn
    • genetically determined abnormal reactivity to a chemical
    • reaction to chemical that general population doesn't have
    • 5% or less
  20. Immediate vs. Delayed Toxicity
    • imm: overdose by drinking gasoline, no time passes
    • delay: exposed but not show effects until time passes, Ex. cancer
  21. Reversible vs. Irreversible toxic effects
    • rev: tylenol destroying liver cells, they regenerate if treated
    • irr: higher doses of tylenol and alcohol causes permenant liver damage, fatty liver pscerosis
  22. Local vs. Systemic
    • local: hydrogen peroxide on skin, or skin rash
    • systemic: sulfa drugs or penicillins.
  23. Interaction of Chemicals
    • additive: 2+3=5
    • synergistic: 2+3 = 20
    • potentiation: 0+3=10
    • antagonism
  24. Types of antagonism
    • functional
    • chemical/inactivation
    • dispositional
    • receptor
  25. Tolerance
    body becomes less sensitive to a substance
  26. Route and Site of exposure
    • gastrointestinal tract: ingestion, bad mushrooms
    • lungs: inhalation, perfumes
    • skin: topical or dermal
    • Parenteral: other than intestinal canal, IV drugs given the wrong conc
  27. Duration and frequency of exposure
    • acute
    • subacute
    • subchronic
    • chronic
  28. Functional antagonism
    2 drugs offset each other effecting physiological changes
  29. Chemical antagonism
    • chemical rxn between 2 things that renders them usless or less toxic
    • ex: chelating agents
  30. Dispositional antagonism
    something effects ADME of drug and its effects are diminished
  31. Receptor antagonism
    2 chemicals bind to same receptors and produces a lower effect
  32. absorption
    administered --> into systemic circulation
  33. distribution
    systemic circulation --> into tissue
  34. Biotransformation
    systemic circulation --> metabolized or excreted
  35. drug conc at site of action/receptor interaction--->
    pharmacological effect
  36. Pharmacological effect -->
    • clinical response
    • toxicity
  37. Clinical response-->
    • toxicity
    • efficacy
  38. 1st pass mechanism
    • goes to the liver to be metabolized
    • inactivate it
    • activate it
    • or do nothing
  39. Zero order kinetics
    • rate remains constant and is independent of concentartions or amount of chemical
    • biological system is rate limiting
    • t1/2: increases with dose (not a true t1/2)
    • alcholol metabolized by this
  40. First-order kinetics
    • rate proportional to concentration or amount of chemical present
    • chemical is rate limiting
    • T1/2: independent of dose (true t1/2)
    • most chemicals in the body are metabolized this way
  41. At high concentrations the biological system may.......(kinetics
    become saturated and change from firstorder to zero order
  42. K(el): elimination rate constant
    amount or concentration changes by fraction per unit of time
  43. Dose response relationships
    • Therapeutic index(TI)
    • ED50
    • TD50
    • LD50
  44. Therapeutic Index (TI)
    • safe operation window
    • area where you expect drugs to work
  45. ED50
    • effective dose that produces response in 50% of people
    • animal or human
  46. TD50
    • Toxic dose expect to see in 50% of population
    • animal or human
  47. LD50
    lethal dose observed in 50% of ANIMALS!
  48. NOAEL
    no observed adverse effect level
  49. dose response vs. toxicity
    • as dose increases
    • noael-->TI-->Toxicity-->death
    • 0-250-->250-500-->500-2500-->2500 and above
  50. below the region of homeostasis
  51. above the region of homeostasis
    • toxicity
    • and threshold for adverse effects
    • eventually death
  52. molecular mechanism
    we identify the specifec target molecule which is attacked by toxin
  53. Nonspecific toxin
    eats up whatever it sees
  54. Specific toxin
    • attack a specific target
    • inital attack leads to cascade of events that will lead eventually to toxicity
  55. Two types of toxicities
    • linked to target molecule that is damaged: vapor attack retina of eye, causes blindness, immediate toxicity
    • a sequence of complexities: compound destroys pancrease, no immediate toxicity but diabetes eventually creates toxicity
  56. Symptom of toxicity may....(two things)
    • relate directly to the interaction between the toxicant and its specific target molecule
    • may be comlicated by secondary effects
  57. the precise molecular site of action of many compounds has been identified while....
    for the majority of toxicants, site(s) remain(s) unknown
  58. toxicity caused by drugs/chemicals may....
    result through a chain of events which begins with an action at a very specific target
  59. Target molecules of carcinogens
    • proteins
    • lipids
    • nucleic acids (RNA, DNA)
  60. Specific proteins that are target of toxins
    • enzymes
    • mitochondrial respiratory chain
    • receptors/ion channels
    • transport proteins
  61. organophosphates
    replace acetylcholine to cause toxicity
  62. Process of organophosphate toxicity
    • acetylcholenesterase acts on organophosphates like it is acetylcholine
    • acetylcholenesterase ends up with phosphate group at end and the enzyme cant recover easily from this toxic effect
  63. What happens to acetylcholenesterase in the presence of water?
    Is is recovered and makes free acetate, after it destroys acetylcholine
Card Set
Toxicology Test 1
Toxicology UMKC Test 1