Pharmacology Exam 1

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Author:
Rx2013
ID:
59581
Filename:
Pharmacology Exam 1
Updated:
2011-01-13 11:04:30
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Intro Chemotherapy
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Intro to chemotherapy I
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  1. Chemotherapy is the use of drugs to eradicate a parasite
    with minimal harm to the host organism
  2. Parasites include
    • viruses
    • bacteria
    • fungi
    • protozoa
    • insects
    • cancer cells
  3. Characteristics of chemotherapeutic agents
    • more toxic to parasite than host
    • targets biochemical or physiological differences
    • restricted distribution of the drug to the infected area
  4. Effectiveness of chemotherapy is related to
    the extent of differences between the parasite and the host
  5. for less selective drugs
    • use higher doses
    • more toxic to host
  6. bacterial chemotherapy is generally ____ ____ than cancer chemotherapy
    more successful
  7. Kirby bauer disc diffusion test
    bigger zone of inhibition = better efficacy of the drug
  8. MIC
    minimal inhibitory concentration
  9. MBC
    minimal bacteriocidal concentration
  10. Log cell kill
    drug kills a fixed fraction of parasitic cells
  11. Log cell kill =
    -log10 (surviving fraction)
  12. if one cell in a million survives (surviving fraction 10-6 )
    6 log kill
  13. log kill to kill everything in the body
    7 log kill
  14. Total cell kill concept is usually not used because of
    toxicity
  15. 3 log kill, 1 log regrowth used in
    cancer chemotherapy
  16. 5 major targets of chemotherapy
    • inhibition of cell wall synthesis
    • inhibition of protein synthesis
    • inhibition of nucleic acid replication & transcription
    • inhibition of synthesis of essential metabolites
    • injury to plasma cell membrane
  17. Drugs that inhibit cell wall synthesis
    • PCN
    • Cephalosporins
    • bacitracin
    • vancomycin
  18. Drugs that inhibit protein synthesis
    • chloramphenicol
    • erythromycin
    • tetracyclines
    • streptomycin
  19. Drugs that inhibit nucleic acid replication and transcription
    • quinolones
    • rifampin
  20. drugs that cause injury to plasma membrane
    polymyxin B
  21. Drugs that inhibit synthesis of essential metabolites
    • sulfanilamide
    • trimethoprim
  22. If there is no immune response
    • drugs may have to kill every parasitic cell
    • cancer
  23. Reasons for absence of immune response
    • impaired immune system (aids)
    • use of immunosuppressant drugs (inhibition of Tcell activation)
    • parasite evasion of immune response (helminths)
    • parasite does not evoke immune response (cancer)
  24. The basis of chemotherapy is that:
    A. a drug needs to be more toxic to the parasite than the host.
    B. A& B
    C. A drug needs to enhance immune response
    D. There needs to be a mechanistic difference between parasite and host cells
    E. None of the above
    B. A&B
    (this multiple choice question has been scrambled)
  25. If two drugs are given simultaneously or successively and thier mechanisms of action are independant, their log cell kill is
    additive
  26. If two drugs are given simultaneously or successively and their mechanisms are complementary the log cell cill may be
    synergistic
  27. FIC index =
    (MIC A + B)/A + (mic B+A)/B
  28. FIC = 1
    additive
  29. FIC < 1
    synergistic
  30. FIC > 1
    antagonistic
  31. Advantages of combo chemotherapy
    • treatment of mixed bacerial infections
    • therapy of severe infection of unknown cause
    • prevention of resistance
  32. Disadvantages of combo chemotherapy
    • toxicity
    • misuse of antibiotics
    • treatment of untreatable disease
    • treatment of fever of unknon cause
    • improper dosage
  33. Combo therapy for TB
    4-5 drugs for 6 months
  34. combotherapy for HIV-1
    life time therapy
  35. Mechanisms of drug resistance
    • transformation
    • conjugation
    • transduction
  36. Transformation
    bacterial cell lysis upon death releases mutated DNA which travels to healthy bacteria
  37. Conjugation
    one cell creates resistance and fuses with another to transfer mutated DNA
  38. Transduction
    mutated DNA transfered through a viral particle
  39. Sites of drug resistance
    • drug uptake
    • drug efflux
    • increased rate of drug inactivation
    • altered amount or decreased affinity of target receptor
  40. Decreased drug uptake
    • methotrexate (cancer)
    • Chloroquine (bacterial)
  41. Increased efflux of the drug
    • drugs for TB and Cancer
    • MRP and ABC
  42. increased rate of drug inactivation example
    penicillinase (beta lactamase) in bacteria
  43. Altered amount or decreased affinity of target receptors examples
    • high levels of dihydrofolate reductase (tumor and methotrexate)
    • RNA polymerase fails to bind rifampicin (streptomyces)
  44. Toxicity
    • limiting factor
    • independent of therapeutic mechanisms
  45. Therapeutic index
    LD50/ED50
  46. Standard safety margin (SSM)
    LD1-ED99/ED99
  47. SSM vs TI
    SSM is more useful
  48. Larger margin between ED99 and LD1 =
    better drug
  49. % of drugs eliminated during testing due to toxicity
    31%
  50. Cyclophosphamide may be given by what routes?
    • intravenous
    • oral
  51. Cyclophosphamide is a prodrug activated by
    CYP2D6 in the liver
  52. CYP450 based Gene directed enzyme prodrug therapy allows for
    • localized delivery of drug to effected cells
    • drug is activated at the target cell not in liver
    • effects neighboring cells but not entire body
    • increased efficacy

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