MALIGNANCY DRUGS

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MALIGNANCY DRUGS
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2010-03-24 15:43:47
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MALIGNANCY DRUGS- Pharm test 2
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  1. Genetics

    -________ cause cells to become malignant in several ways
    -________ are normal genes that are involved in the controlled growth, division and death (________) of cells
    -An oncogene is a mutation in a ________.
    -An abnormal oncogene can effect cell growth control proteins & trigger ________ cell division.
    Genetics

    • -Genes cause cells to become malignant in several ways
    • -Protooncogenes are normal genes that are involved in the controlled growth, division and death (apoptosis) of cells
    • -An oncogene is a mutation in a protooncogene.
    • -An abnormal oncogene can effect cell growth control proteins & trigger unregulated cell division.






  2. Genetics

    -Tumor suppressor genes (________) signal a cell to cease multiplying and act to stop the action of ________.
    -If the tumor suppressor genes become lost or dysfunctional cells can reproduce________.
    -Other genes repair ________ damage.
    -If these are damages, mutations are not repaired and passed to the next ________ or daughter cells.
    Genetics

    • -Tumor suppressor genes (antioncogenes) signal a cell to cease multiplying and act to stop the action of oncogenes.
    • -If the tumor suppressor genes become lost or dysfunctional cells can reproduce uncontrollably.
    • -Other genes repair DNA damage.
    • -If these are damages, mutations are not repaired and passed to the next generation or daughter cells.





  3. Genetics

    -Since it takes time for enough cell mutation to occur and cancer is more likely to occur in ________ individuals.
    Genetics

    -Since it takes time for enough cell mutation to occur and cancer is more likely to occur in older individuals.





  4. Cell cycle & Chem

    -Chemo causes cell ________ by interfering with cell ________
    -Cell cycle non-specific (CCNS) drugs act during ________ phase of the cell cycle.
    -Cell cycle specific (CCS) drugs act during a _______ phase of the cell cycle.
    -________ are more effective against rapidly growing cancer cells.
    Cell cycle & Chem

    • -Chemo causes cell death by interfering with cell replication
    • -Cell cycle non-specific (CCNS) drugs act during any phase of the cell cycle.
    • -Cell cycle specific (CCS) drugs act during a specific phase of the cell cycle.
    • -CCS are more effective against rapidly growing cancer cells.




  5. Drugs

    -________
    -________ agents (Some are CCS)
    -________antibiotics
    -________
    -________
    -Anti________
    -________ inhibitors
    Drugs

    • -CCNS
    • -Alkylating agents (Some are CCS)
    • -Anti-tumor antibiotics
    • -Hormones
    • -CCS
    • -Antimetabolites
    • -Mitotic inhibitors




  6. Growth Fraction & Doubling Time

    -________ factors that play a major role in response of cancer to chemo
    -Growth ________is the number of cells proliferating within the tumor
    -________ is more effective against cells that have a high growth fraction
    -Small and early cancer cells and fast-growing tumors respond well to ________ with a ________ cure rate.
    Growth Fraction & Doubling Time

    • -Two factors that play a major role in response of cancer to chemo
    • -Growth fraction is the number of cells proliferating within the tumor
    • -Chemo is more effective against cells that have a high growth fraction
    • -Small and early cancer cells and fast-growing tumors respond well to chemo with a higher cure rate.




  7. Growth & Chemo

    -Growth is usually faster in ________ stages of tumor development
    -As tumor grows that blood supply ________-> ________ growth rate
    -Chemo is moat effect in ________ tumors with sufficient ________ supply.
    -As tumor enlarges its growth fraction ________ and doubling time________--> ________ effectiveness of chem
    Growth & Chemo

    • -Growth is usually faster in early stages of tumor development
    • -As tumor grows that blood supply decrease-> slower growth rate
    • -Chemo is moat effect in young tumors with sufficient blood supply.
    • -As tumor enlarges its growth fraction decrease and doubling time increase--> decreased effectiveness of chem




  8. Chemo

    -Non-selective so both ________ & ________cells are affected
    -Side effects are mostly related to toxic effects on ________ cells
    -Chemo is effective because healthy cells repair ________ and continue to ________.
    -So, side effects of chemo are generally ________.
    Chemo

    • -Non-selective so both healthy & malignant cells are affected
    • -Side effects are mostly related to toxic effects on normal cells
    • -Chemo is effective because healthy cells repair themselves and continue to grow.
    • -So, side effects of chemo are generally temporary.




  9. Types of Therapy

    -Adjuvant therapy?
    -Neo-adjuvant therapy?
    -Palliative therapy?
    Types of Therapy

    • -Adjuvant therapy-used after another tx
    • -Neo-adjuvant therapy-used first to shrink tumor so it can be removed by surgery
    • -Palliative therapy-used to relieve symptoms associated with advanced disease



  10. Protocols

    -Chemo administration is guided by specific ________ that were developed based on the results of controlled ________ studies.
    -The length of treatment is determined by type of ________, extent of ________, type of ________, excepted ________ effects of the drugs.
    -Usually given in ________ to increase chance of ________ cells and allowing normal ones to ________.
    Protocols

    • -Chemo administration is guided by specific protocols that were developed based on the results of controlled research studies.
    • -The length of treatment is determined by type of chemo, extent of malignancy, type of chemo, excepted side effects of the drugs.
    • -Usually given in cycles to increase chance of killing cells and allowing normal ones to recover.



  11. Protocols

    -The ________, ________and ________ of cycles of chemo are based upon ________ & ________ of tumor , whether disease has metastasized and the condition of the patient.
    -________ may consist of one drug or combination
    -Duration of each treatment varies from________ to ________ and may be repeated weekly, biweekly, or monthly.
    Protocols

    • -The duration, frequency and number of cycles of chemo are based upon types & size of tumor , whether disease has metastasized and the condition of the patient.
    • -Chemo may consist of one drug or combination
    • -Duration of each treatment varies from minutes to days and may be repeated weekly, biweekly, or monthly.
  12. New Developments & Protocols



    -________ chemo protocols have been used mostly recently
    -The interval between successive dose of chemo is ________ which has--> improved ________
    New Developments & Protocols

    • -Dose dense chemo protocols have been used mostly recently
    • -The interval between successive dose of chemo is shortened which has--> improved survival



  13. Drug Resistance

    -Malignant tumors can develop resistance to ________
    -Multidrug resistance (________) can occur for several reasons:
    -1. drug may not kill ________& cells may ________ & become resistance.
    -2.________ resistance of some tumor cells.
    Drug Resistance

    • -Malignant tumors can develop resistance to chemo
    • -Multidrug resistance (MDR) can occur for several reasons:
    • -1. drug may not kill cells & cells may mutate & become resistance.
    • -2. natural resistance of some tumor cells.



  14. Combo Chemo

    -Combinations of chemo have consistently shown to be more effective than ________ therapy
    -Chemo is most effective when it kills cells in ________ phases of the cell cycles.
    -Combo therapy makes this more likely to occur.
    -________ & ________ are often combined
    -Each drug should have a different mode of ________ & different dose-limiting________.
    Combo Chemo

    • -Combinations of chemo have consistently shown to be more effective than monodrug therapy
    • -Chemo is most effective when it kills cells in all phases of the cell cycles.
    • -Combo therapy makes this more likely to occur.
    • -CCS & CCNS are often combined
    • -Each drug should have a different mode of action & different dose-limiting toxicities.



  15. General Adverse Reactions to Chemo

    -1. ________ suppression:
    -________, ________,________
    - 2. ________
    -Anorexia, N&V, diarrhea, ________
    -3. ________
    -4. ________
    -5. ________
    General Adverse Reactions to Chemo

    • -1. Bone marrow suppression:
    • -Anemia, neutropenia, thrombocytopenia
    • - 2. GI
    • -Anorexia, N&V, diarrhea, mucoitis
    • -3. Alopecia
    • -4. Fatigue
    • -5. Infertility
  16. Activities of Chemotherapy

    -Chemo works on the principles of first order _________. That is, the number of tumor cells _________ is proportionate to the _________ administered.
    -The number of cells_________ is a constant percent of the total number of cancer cells _________
    -Examples: If there are 10 malignant cells present and the drug kills 80 percent of the cells then with the first dose, 8 will be killed. 80% of the remaining cells can be excepted to be killed with the second dose. However, the cells are _________during the process.
    Activities of Chemotherapy

    • -Chemo works on the principles of first order kinetics. That is, the number of tumor cells killed is proportionate to the dose administered.
    • -The number of cells killed is a constant percent of the total number of cancer cells present.
    • -Examples: If there are 10 malignant cells present and the drug kills 80 percent of the cells then with the first dose, 8 will be killed. 80% of the remaining cells can be excepted to be killed with the second dose. However, the cells are reproducing during the process.
  17. Chemotherapy


    -Chemo is most effective against cells with a fast ________ rate and ________
    - ________ cells, ____ cells and ________ cells have growth rates equal to most cancer cells.
    -Most chemo has some degree of ________ to those cells.
    -Major toxicity is ________ or ________ supression
    -> anemia, leukopenia and thrombocytopenia
    -The ________ (height of suppression ) takes about __-___weeks to develop
    -To limit toxicities the drugs are given in a ________ allowing ________ in between doses.
    Chemotherapy

    • -Chemo is most effective against cells with a fast metabolic rate and reproduction
    • -Bone marrow cells, GI cells and skin cells have growth rates equal to most cancer cells.
    • -Most chemo has some degree of toxicity to those cells.
    • -Major toxicity is myelosupression or bone marrow supression -> anemia, leukopenia and thrombocytopenia
    • -The nadir (height of suppression ) takes about 1-2 weeks to develop
    • -To limit toxicities the drugs are given in a series allowing recovery in between doses.
  18. Alkylating Agents

    -________-kills cells in various & multiple stages of the cell cycle
    -Most effective in ________ (________ phase)
    -Several classifications in the group:
    -1. Mustard gas derivatives (________)
    -2. Nitrosureas (________)
    -3. Alkyl sulfonates (________)
    -4. Alkylating like drugs (________)
    Alkylating Agents

    • -CCNS-kills cells in various & multiple stages of the cell cycle
    • -Most effective in G0 (resting phase)
    • -Several classifications in the group:
    • -1. Mustard gas derivatives (Cytoxan)
    • -2. Nitrosureas (carmustine)
    • -3. Alkyl sulfonates (Myleran)
    • -4. Alkylating like drugs (cisplatin)
  19. Cytoxan

    -Major problem is that Cytoxan is a severe _________ that can cause tissue _________
    -Must be given through patent _________ line if given _______
    -Patient must be well hydrated to prevent hemorrhage _________
    -MESNA is a _________ often given with high dose _________ to inactivate urotoxic metabolites in bladder to minimize injury-_________ suppression &_________ are common.
    Cytoxan

    • -Major problem is that Cytoxan is a severe vesicant that can cause tissue necrosis
    • -Must be given through patent IV line if given IV
    • -Patient must be well hydrated to prevent hemorrhage cystitis
    • -MESNA is a cytoprotectant often given with high dose cytocan to inactivate urotoxic metabolites in bladder to minimize injury
    • -Bone marrow suppression & alopecia are common.
  20. Dealing with Extravastion

    -The urea usually becomes _________ and _________ may occur
    -If leakage of dug is obvious, prompt infiltration of the area with sterile _________ sodium _________ and application of an _________ compress for ___to_____ hours may minimize the local reaction
    Dealing with Extravastion

    • -The urea usually becomes indurated and sloughing may occur
    • -If leakage of dug is obvious, prompt infiltration of the area with sterile isotonic sodium thiosulfate and application of an ice compress for 6 to 12 hours may minimize the local reaction
  21. Cytoxan & Herbs

    -Avoid: Garlic ( _________), ginkgo (__________________), echinacea (_________), ginseng (_________), St. John's Wort (_________), kava kava (_________)
    Cytoxan & Herbs

    -Avoid: Garlic ( antiplatelet), ginkgo (increased antiplatelet activity), echinacea (decreased effect of immunosuppressive drugs), ginseng (alters bleeding time), St. John's Wort (interferes with chemo), kava kava (increased risk of bleeding)
  22. Antimetabolites

    -Resemble natural metabolites which_________, _________ and _________ organic compounds for use by the body.
    -Antimetabolites disrupt _________ processes and can inhibit _________ synthesis
    -Classified as _________ and work during the _________ phase (_________ sythesis & metabolism) of cycle.
    Antimetabolites

    • -Resemble natural metabolites which synthesize, recycle and breakdown organic compounds for use by the body.
    • -Antimetabolites disrupt metabolic processes and can inhibit enzyme synthesis
    • -Classified as CCS and work during the S phase (DNA sythesis & metabolism) of cycle.
  23. Antimetabolites

    -Classifed according to the substance with which they interfere:
    -Methotrexate -_________ antagonist
    -5-FU- _________ antagonist
    -6 mercaptopurine- _________ antagonist
    -Fludara- _________ inhibitors
    Antimetabolites

    • -Classifed according to the substance with which they interfere:
    • -Methotrexate -folic acid antagonist
    • -5-FU- pyrimidine antagonist
    • -6 mercaptopurine- purine antagonist
    • -Fludara- adenosine deaminase inhibitors
  24. Drug interactions

    -Numerous drugs interact with antimetabolites including _________, _________, _________, _________ inhibitors & _________ herbs.
    Drug interactions

    -Numerous drugs interact with antimetabolites including ASA, NSAIDS, BACTRIM, COX-2 inhibitors & OTC herbs.
  25. Antitumors Antibiotics

    -_________-severe cardiactoxic effects - must be given with caution
    -_________ function must be assessed prior to use
    .-_________ causes pneumonitis-> pulmonary _________
    Antitumors Antibiotics

    • -Adriamycin-severe cardiactoxic effects - must be given with caution
    • -Cardiac function must be assessed prior to use.
    • -Bleomycin causes pneumonitis-> pulmonary fibrosis

  26. Mitotic Inhibitors (Plant Alkaloids)

    -______- block cell division at the ______ phase (mitotic phase) of the cell cycle
    -______ alkaloids- "neuro twins" ______ & ______, ______l
    -Cause ______ alopecia, constipation, N&V, diarrhea, reversible & irreversible ______.
    -Watch for ______ of fingers & toes "______ syndrome"
    Mitotic Inhibitors (Plant Alkaloids)

    • -CCS- block cell division at the M phase (mitotic phase) of the cell cycle
    • -Vinca alkaloids- "neuro twins" Vinblastine & vincristine, Paciltaxel
    • -Cause leukopenia, alopecia, constipation, N&V, diarrhea, reversible & irreversible neurotoxicity.
    • -Watch for tingling of fingers & toes "stocking/glove syndrome"

  27. Liposomal Chemo

    -Chemo packaged inside synthetic ______ globules called ______
    -Fatty coating helps the chemo remain in the system ______ & ______ the side effects ( alopecia, N&V, cardiac toxicity) & ______ duration of therapeutic effects
    -Encapsulated doxrubicin-______& ______- TCS
    Liposomal Chemo

    • -Chemo packaged inside synthetic fat globules called liposomes
    • -Fatty coating helps the chemo remain in the system longer & decrease the side effects ( alopecia, N&V, cardiac toxicity) & increase duration of therapeutic effects
    • -Encapsulated doxrubicin-Doxil & vincristie- TCS

  28. Hormonal Chemo

    -______
    -Anti______
    -Anti______
    -Sex ______
    -______-releasing hormone analogue.
    Hormonal Chemo

    • -Not true chemo they are used to treat cancer
    • -Corticosteroids
    • -Antiestrogens
    • -Antiandrogens
    • -Sex hormones
    • -Gonadotrophin-releasing hormone analogue.

  29. Hormonal Chemo

    -1.Corticosteroids suppress ______ that occurs as a result of tumor growth.
    -2. Sex hormones-______ & ______ - used to slow growth of hormonally dependent tumors (______ & ______) Estrogen is used to palliate ______ cancer in men & slow the growth of some ______ cancers in women.
    Hormonal Chemo

    • -1.Corticosteroids suppress inflammation that occurs as a result of tumor growth.
    • -2. Sex hormones-estrogen & androgen - used to slow growth of hormonally dependent tumors (prostate & breast) Estrogen is used to palliate prostate cancer in men & slow the growth of some breast cancers in women.
  30. H
    Hormonal Chemo

    • -Progestins may be used in breast, endometrial & renal ca. Can cause fluid retention the clotting disorders.
    • -Androgens- given to premenopausal women with advanced breast CA - will --> masculine secondary sex characteristics
    • -Antiestrogens (tamoxifen) used to treat breast ca that is estrogen-receptor positive.
  31. T
    Tamoxifen

    • -Has been shown to prevent recurrence in pre & post menopausal women
    • -Side effects include: flushing, irregular periods, headaches, N&V
    • -In women increase the risk of developing cancer of the uterus
  32. A
    Antiandrogens

    -Casodex- used to treat men with hormone-responsive prostate cancer.
  33. A
    Aromatase Inhibitors

    • -Post menopause, the androgen is converted to estrogen
    • -Aromatase inhibitors block the peripheral conversion of androgen to estrogen --> suppression post menopausal synthesis of estrogen
    • -Used in the treatment of hormonally sensitive breast cancer in post menopausal women & premenopausal women who have had their ovaries removed.
  34. T
    Targeted therapies to treat cancer

    • -New approach to cancer treatment
    • -Work by interfering with cancer cell growth and division in different ways and at various points in the development, growth & spread of cancer
    • -Blocking signals that tell cancers cells to grow & divide uncontrollably, targeted cancer therapies can help stop the growth & division of cancer cells.
  35. D
    Downstream Signal Transduction

    • -Transmission of signals may come from outside the cell as a growth factor protein (ligand) which binds to a receptor activating it or intracellularly where kinase (transfer enzyme) activity takes place
    • -These treatments are controversial & expensive up to $ 30K per year.
  36. T
    Toposiomerase I & II inhibitors

    • -Toposiomerase I inhibitors- affect S phase (Synthesis of DNA ) Hycamtin is used for metastatic colorectal cancer & refractory ovarian cancer
    • -Toposiomerase II inhibitors- work on G2 phase (cell prepares for mitosis) of cell reproduction. Etoposide given for small cell lung ca and testicular ca.
  37. T
    Tyrosine Kinase Inhibitors

    • -Protein tyrosine kinases is a family of proteins that regulate cell growth, proliferation & angiogenesis
    • -These proteins are involved in normal and malignant cell growth
    • -These agents act on tumor & tumor vasculature
    • -Tarceva is used to treat locally advanced or metastatic non-small cell lung ca after failure of one chemo regimen
  38. P
    Proteasome Inhibitors

    • -Intracellular multienzymes that degrade proteins to eliminate cells of proteins that are not needed
    • -Velcade alters proteins that regulate cell growth & division
    • -used for multiple myeloma, colorectal & lung ca
    • -Cancer cells are more sensitive to proteasomes than normal cells
  39. M
    Multikinase Inhibitors

    • -Newest drug approved to treated advanced renal cell ca which has a very poor prognosis
    • -Nexavar can cause HTN along with cracking of skin on palms & soles and stomatitis
  40. A
    Angiogenesis Inhibitors

    • -Angiogenesis is the development of new capillaries
    • -Critical for tumor growth & metastic disease
    • -Angiogenesis inhibitor inhibit the formation of blood vessels needed for tumor growth & mets
    • -Avstin is used for metastatic ca of the colon & rectum

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