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Boards Pharm 11: Hem/Onc > Oncology > Flashcards

Oncology Flashcards

1
Q

Antimetabolites - Available Drugs

A
  • Methotrexate (MTX)
  • 5-Fluorouracil (5-FU)
  • 6-Mercaptopurine (6-MP)
  • 6-Thioguanine (6-TG)
  • Cytarabine (ara-C)
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2
Q

Antimetabolites - Cell Cycle Specificity

A

All anti metabolites inhibit DNA synthesis and are thus S phase specific.

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3
Q

Methotrexate (MTX) - MOA

A
  • S phase specific
  • Folic acid analog that inhibits dihydrofolate reductase –> Inhibit production of dTMP –> Inhibit DNA and protein synthesis
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4
Q

Methotrexate (MTX) - Clinical Use

A

Cancer:

  • Leukemia
  • Lymphoma
  • Choriocarcinoma
  • Sarcoma

Non-neoplastic

  • Abortion
  • Ectopic pregnancy
  • Rheumatoid arthritis
  • Psoriasis
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5
Q

Methotrexate (MTX) - Toxicities

A
  • Myelosuppression - Reversible with Leucovorin (folinic acid) rescue
  • Macrovesicular fatty changes in liver
  • Mucositis (eg GI mucosa)
  • Teratogenic
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6
Q

5-Fluorouracil (5-FU) - MOA

A
  • S phase specific
  • Pyrimidine analog that is bioactivated to 5F-dUMP which covalently complexes folic acid –> Complex inhibits thymidylate synthase –> Inhibit production of dTMP –> Inhibit DNA and protein synthesis
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7
Q

5-Fluorouracil (5-FU) - Clinical Use

A
  • Colon cancer and other solid tumors
  • Topical for basal cell carcinoma
  • Synergistic with MTX
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8
Q

5-Fluorouracil (5-FU) - Toxicities

A
  • Myelosuppression which is not reversible with leucovorin (leucovorin actually increases the effects of 5-FU)
  • The rescue for 5-FU overdose is Thymidine
  • Photosensitivity
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9
Q

6-Mercaptopurine (6-MP) - MOA

A
  • S phase specific
  • Same MOA as 6-TG
  • Purine (thiol) analog bioactivated by HGPRTase (ie the enzyme that converts Hypoxanthine and Guanine to IMP and GMP in the purine salvage/degredation pathway) –> Inhibits purine synthesis
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10
Q

6-Mercaptopurine (6-MP) - Clinical Use

A
  • Leukemias
  • Lymphomas
  • Not for CLL or Hodgkin’s Lymphoma
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11
Q

6-Mercaptopurine (6-MP) - Toxicities

A
  • Bone marrow suppression
  • GI mucosa
  • Liver toxicity
  • Metabolized by Xanthine oxidase (ie Another enzyme in the purine salvage/degredation pathway that degrades hypoxanthine and xanthine to xanthine and uric acid respectively) –> Increased toxicities when administered with Allopurinol (i.e. a Xanthine oxidase inhibitor)
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12
Q

6-Thioguanine (6-TG) - MOA

A
  • S phase specific
  • Same MOA as 6-MP
  • Purine (thiol) analog bioactivated by HGPRTase (ie the enzyme that converts Hypoxanthine and Guanine to IMP and GMP in the purine salvage/degredation pathway) –> Inhibits purine synthesis
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13
Q

6-Thioguanine (6-TG) - Clinical Use

A
  • Acute lymphoblastic (/lymphocytic, /lymphoid) leukemia (/lymphoma) - ALL
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14
Q

6-Thioguanine (6-TG) - Toxicities

A
  • Bone marrow depression
  • Liver toxicity
  • Can be given with Allopurinol (i.e. a Xanthine oxidase inhibitor)
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15
Q

Cytarabine (ara-C) - MOA

A
  • S phase specific
  • Pyramidine analog inhibit DNA polymerase
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16
Q

Cytarabine (ara-C) - Clinical Use

A
  • AML
  • ALL
  • High grade non-Hodgkin’s lymphoma
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17
Q

Cytarabine (ara-C) - Toxicities

A
  • Leukopenia
  • Thrombocytopenia
  • Megaloblastic anemia
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18
Q

Antitumor Antibiotics - Available Drugs

A
  • Dactinomycin (Actinomycin D)
  • Doxorubicin (Adriamycin) / Daunorubicin
  • Bleomycin
  • Etoposide (VP-16) / Teniposide
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19
Q

Dactinomycin (Actinomycin D) - MOA

A
  • No cell cycle specificity
  • Intercalates in DNA
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20
Q

Dactinomycin (Actinomycin D) - Clinical Use

A

Used for childhood tumors:

  • Wilm’s tumor
  • Ewing’s sarcoma
  • Rhabdomyosarcoma

“Dactinomycin - Children act out”

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21
Q

Dactinomycin (Actinomycin D) - Toxicities

A
  • Myelosuppression
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22
Q

Doxorubicin (Adriamycin) / Daunorubicin - MOA

A
  • No cell cycle specificity
  • Generate free radicals
  • Non-covalently intercalate in DNA –> create DNA breaks –> decrease replication
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23
Q

Doxorubicin (Adriamycin) / Daunorubicin - Clinical Use

A
  • Hodgkin’s lymphomas
  • Myelomas
  • Sarcomas
  • Solid tumors (breast, ovary, lung)
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24
Q

Doxorubicin (Adriamycin) / Daunorubicin - Toxicities

A
  • Dilated cardiomyopathy
  • myelosuppression
  • Alopecia
  • Extravasation is toxic
  • Dexrazoxane (i.e. an iron chelating agent) can be used to prevent the cardiotoxicity
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25
Q

Bleomycin - MOA

A
  • G2 phase specific
  • Induce free radical formation –> DNA breaks
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26
Q

Bleomycin - Clinical Use

A
  • Testicular cancer
  • Hodgkin’s lymphoma
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27
Q

Bleomycin - Toxicities

A
  • Pulmonary fibrosis
  • Skin changes
  • Minimal myelosuppression
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28
Q

Etoposide (VP-16) / Teniposide - MOA

A
  • S-G2 phase specific
  • Inhibit topoisomerase II –> DNA degredation
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29
Q

Etoposide (VP-16) / Teniposide - Clinical Use

A
  • Small cell carcinoma of the lung and prostate
  • Testicular carcinoma
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30
Q

Etoposide (VP-16) / Teniposide - Toxicities

A
  • Myelosuppression
  • GI irritation
  • Alopecia
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31
Q

Alkylating Agents - Available Drugs

A
  • Cyclophosphamide / Ifosfamide
  • Nitrosoureas (Carmustine [BCNU], Lomustine [CCNU], Semustine [meCCNU], Streptozotocin[STZ])
  • Busulfan
32
Q

Cyclophosphamide / Ifosfamide - MOA

A
  • No cell cycle specificity
  • Nitrogen Mustards
  • Same action as the Nitrosoureas and Alkyl Sulfonates
  • Covalently X-link (interstrand) DNA at Guanine N-7
  • Requires bioactivation in the liver
33
Q

Cyclophosphamide / Ifosfamide - Clinical Use

A
  • Non-Hodgkin’s lymphoma
  • Breast carcioma
  • Ovarian carcinoma
  • Also function as immunosuppressants
34
Q

Cyclophosphamide / Ifosfamide - Toxicities

A
  • Myelosuppression
  • Hemorrhagic cystitis - can be partially prevented with administration of Mesna (i.e. thiol group of mesna binds toxic metabolites)
35
Q

Nitrosoureas - Available Drugs

A
  • Streptozocin (STZ)
  • Carmustine (BCNU)
  • Lomustine (CCNU)
  • Semustine (meCCNU)
36
Q

Nitrosoureas - MOA

A
  • No cell cycle specificity
  • Same action as the Nitrogen Mustards and Alkyl Sulfonates
  • Covalently X-link (interstrand) DNA at Guanine N-7
  • Requires bioactivation in the liver
  • Can cross the BBB –> CNS

[BCNU, CCNU, meCCNU, STZ]

37
Q

Nitrosoureas - Clinical Use

A
  • Brain tumors, including Glioblastoma multiforme

[BCNU, CCNU, meCCNU, STZ]

38
Q

Nitrosoureas - Toxicities

A

CNS toxicities

  • Dizziness
  • Ataxia

[BCNU, CCNU, meCCNU, STZ]

39
Q

Busulfan - MOA

A
  • No cell cycle specificity
  • An Alkyl Sulfonate
  • Same action as the Nitrogen Mustards and Nitrosoureas
  • Covalently X-link (interstrand) DNA at Guanine N-7
40
Q

Busulfan - Clinical Use

A
  • CML
  • Also used to ablate patient’s bone marrow prior to a bone marrow transplantation
41
Q

Busulfan - Toxicities

A
  • Pulmonary fibrosis
  • Hyperpigmentation
42
Q

Cisplatin / Carboplatin - MOA

A
  • No cell cycle specificity
  • Platinum crosslinking compounds
  • Function very similarly to the alkylating agents but lack an alkyl group.
  • Cross-link DNA
43
Q

Cisplatin / Carboplatin - Clinical Use

A
  • Testicular carcinoma
  • Bladder carcinoma
  • Ovarian carcinoma
  • Lung carcinoma
44
Q

Cisplatin / Carboplatin - Toxicities

A
  • Nephrotoxicity
  • Acoustic nerve damage
  • Prevent nephrotoxicity with Amifostine (i.e. a free radical scavenger) and chloride diuresis
45
Q

Microtubule Inhibitors - Available Drugs

A
  • Vincristine / Vinblastine
  • Taxols (e.g. Paclitaxel)
46
Q

Vincristine / Vinblastine - MOA

A
  • M phase specific
  • Vinca Alkaloids
  • Bind tubulin and block polymerization of microtubules so that the mitotic spindle cannot form

“Microtubules are the vines of your cells”

47
Q

Vincristine / Vinblastine - Clinical Use

A
  • Hodgkin’s lymphoma
  • Wilm’s tumor
  • Choriocarcinoma
  • ALL
48
Q

Vincristine / Vinblastine - Toxicities

A

Neurotoxicity

  • Areflexia
  • Peripheral neuritis
  • Paralytic ileus

Bone marrow suppression

“Vinblastine Blasts Bone marrow”

49
Q

Paclitaxel - MOA

A
  • M phase specific
  • A Taxol
  • Hyperstabilize polymerized microtubules so the mitotic spindle cannot break down –> no progression to anaphase

“It is taxing to stay polymerized

50
Q

Paclitaxel - Clinical Use

A
  • Ovarian carcinoma
  • Breast carcinoma
51
Q

Paclitaxel - Toxicities

A
  • Myelosuppression
  • Hypersensitivity
52
Q

Hydroxyurea - MOA

A
  • S phase specific
  • Inhibits ribonucleotide reductase –> Decreased DNA synthesis
53
Q

Hydroxyurea - Clinical Use

A
  • Melanoma
  • CML
  • Sickle cell disease (increased HbF)
54
Q

Hydroxyurea - Toxicities

A
  • Bone marrow suppression
  • GI upset
55
Q

Prednisone - MOA

A

May trigger apoptosis, may even work on non-dividing cells

56
Q

Prednisone - Clinical Use

A

Most commonly used glucocorticoid in chrmotherapy

  • CLL
  • Hodgkin’s lymphoma (part of MOPP regimen)
  • Also an immunosuppressant used in autoimmune disease
57
Q

Prednisone - Toxicities

A
  • Cushing’s like symptoms
  • Immunosuppression
  • Cataracts
  • Acne
  • Osteoperosis
  • HTN
  • Peptic ulcers
  • Hyperglycemia
  • Psychosis
58
Q

SERMs - Available Drugs

A
  • Tamoxifen
  • Raloxifene
59
Q

SERMs - MOA

A

Estrogen receptor antagonists in breast tissue

[Tamoxifen, Raloxifene]

60
Q

SERMs - Clinical Use

A
  • Breast cancer
  • Also used in treatment of osteoperosis

[Tamoxifen, Raloxifene]

61
Q

SERMs - Toxicities

A

Tamoxifen

  • Increased risk of endometrial carcinoma due to agonistic effect at endometrium
  • Hot flashes

Raloxifene

  • No risk of endometrial carcinoma - antagonistic at the endometrium
62
Q

Trastuzumab (Herceptin) - MOA

A

Monoclonal antibody against HER-2 (erb-B2) tyrosine kinase

  • Helps mediate killing of HER-2 (+) breast cancer, possibly through antibody dependent cytotoxicity

“Tras-2-zumab”

63
Q

Trastuzumab (Herceptin) - Clinical Use

A

Metastatic breast cancer

64
Q

Trastuzumab (Herceptin) - Toxicities

A
  • Cardiotoxicity
65
Q

Imatinib (Gleevec) - MOA

A

Inhibitor of the bcr-abl tyrosine kinase (i.e. product of the Philadelphia chromosome)

66
Q

Imatinib (Gleevec) - Clinical Use

A
  • CML
  • GI stromal tumors
67
Q

Imatinib (Gleevec) - Toxicities

A
  • Fluid retention
68
Q

Rituximab - MOA

A

Antibody against CD20, which is found in most B cell neoplasms

69
Q

Rituximab - Clinical Use

A
  • Non-Hodgkin’s lymphoma
  • Rheumatoid arthritis (w/ methotrexate)
70
Q

Leucovorin - MOA

A

Folinic acid

  • Gets converted to THF without the need of dihydrofolate reductase
71
Q

Leucovorin - Clinical Use

A
  • Rescue to myelosuppression associated with MTX
  • Enhance the effects of 5-FU
72
Q

Dexrazoxane - MOA

A

Iron chelator –> Reduce the number of iron particals complexed with Anthracyclines (e.g. Doxorubicin, Daunorubicin) –> Lower free radical formation –> Reduce oxidative damage

73
Q

Dexrazoxane - Clinical Use

A

Help prevent the cardiotoxicity of the Anthracyclines (e.g. Doxorubicin, Daunorubicin)

74
Q

Mesna - MOA

A

Thiol group on Mesna binds the toxic metabolites of Cyclophosphamide / Ifosphamide

75
Q

Mesna - Clinical Use

A

Prevent the Hemorrhagic cystitis caused by Cyclophosphamide / Ifosphamide

76
Q

Amifostane - MOA

A

Scavenges toxic metabolites and free radicals

77
Q

Amifostane - Clinical Use

A

Help prevent the nephrotoxicity of the Platinum crosslinking compounds

Boards Pharm 11: Hem/Onc (2 decks)

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