Rapid - Oncology Flashcards Preview

M2 - Pharm Rapid > Rapid - Oncology > Flashcards

Flashcards in Rapid - Oncology Deck (81):
1

Azathioprine

  • Antimetabolite
  • Purine/thiol analog
    • Activated by HGPRT
    • Decreases de novo purine synthesis
    • Metabolized by xanthine oxidase
  • Use:
    • Prevent organ rejection
    • RA
    • IBD
    • SLE
    • weaning off steroids
  • S/E:
    • BM suppression
    • GI/Liver issues
  • Increased toxicity w/Allopurinol, Fexbustat

2

6-mercaptopurine

  • Antimetabolite
  • Purine/thiol analog
    • Activated by HGPRT
    • Decreases de novo purine synthesis
    • Metabolized by xanthine oxidase
  • Use:
    • Prevent organ rejection
    • RA
    • IBD
    • SLE
    • weaning off steroids
  • S/E:
    • BM suppression
    • GI/Liver issues
  • Increased toxicity w/Allopurinol, Fexbustat

3

Cladribine

  • Antimetabolite
  • Purine analog
    • multiple MOAs (DNA polymerase inhibition, DNA strand breaks)
  • Use: Hairy cell leukemia
  • S/E:
    • BM suppression
    • Nephrotoxicity
    • Neurotoxicity

4

Cytarabine (arabinofuranosyl cytidine)

  • Antimetabolite
  • Pyrimidine analog
    • DNA polymerase inhibition
  • Use:
    • Leukemias
    • Lymphomas
  • S/E: BM Suppression + Megaloblastic Anemia
    • (CYTarabine → panCYTopenia)

5

5-fluorouracil

  • Antimetabolite
  • Pyrimidine analog
    • bioactivated to 5-FdUMP
    • covalently complexes folic acid
    • inhibits thymidylate synthase
    • decreases dTMP → DNA synthesis
  • Use:
    • Colon cancer
    • Pancreatic cancer
    • Basal cell carcinoma
  • S/E:
    • BM suppression
    • Hand and Foot syndrome
  • Leucovorin enhances effects, worsens BM suppression

6

Methotrexate

  • Antimetabolite
  • Folic acid analog 
    • competitively inhibits dihydrofolate reductase
    • decreases dTMP → DNA synthesis
  • Use:
    • Leukemias (ALL) / Lymphomas
    • Choriocarcinoma
    • Sarcomas
    • Ectopic/molar pregnancy
    • Medical abortion (+ misoprostol)
    • RA
  • S/E:
    • Reversible BM suppression
    • Hepatotoxicity
    • Mucositis
    • Pulmonary fibrosis

7

Bleomycin

  • Free radical formation → DNA strand breaks
  • Use:
    • Testicular cancer
    • Hodgkin lymphoma
  • S/E:
    • Pulmonary fibrosis (B is Bad for Breathing)
    • Skin hyperpigmentation
  • Minimal BM suppression

8

Dactinomycin (actinomycin D)

  • Intercalates in DNA
  • Use: Childhood tumors
    • Wilms tumor
    • Ewing sarcoma
    • Rhabdomyosarcoma 
  • S/E: BM suppression

9

Doxorubicin

  • Anthracycline
  • Free radical generation
    • Intercalates in DNA → DNA breaks → decreased DNA replication
  • Use:
    • Solid tumors
    • Leukemias
    • Lymphomas
  • S/E:
    • Cardiotoxicity (dilated / fibrosis)
    • Alopecia
    • BM suppression

10

Daunorubicin

  • Anthracycline
  • Free radical generation
    • Intercalates in DNA → DNA breaks → decreased DNA replication
  • Use:
    • Solid tumors
    • Leukemias
    • Lymphomas
  • S/E:
    • Cardiotoxicity (dilated / fibrosis)
    • Alopecia
    • BM suppression

11

Busulfan

  • Alkylating agent
  • Cross-links DNA
  • Use:
    • CML
    • BM ablation before BM transplant
  • S/E:
    • Severe BM suppression
    • Pulmonary fibrosis (B is Bad for Breathing)
    • HypERpigmentation

12

Cyclophosphamide

  • Alkylating agent
  • Cross-links DNA at guanine N-7
    • Bioactivated by liver
    • Toxic Metabolite: Acrolein
  • Use:
    • Solid tumors
    • Leukemia
    • Lymphomas
  • S/E:
    • Hemorrhagic CYstitis
    • BM suppression

13

Ifosfamide

  • Alkylating agent
  • Cross-links DNA at guanine N-7
    • bioactivated by liver
  • Use:
    • Solid tumors
    • Leukemia
    • Lymphomas
  • S/E:
    • Hemorrhagic cystitis
    • BM suppression 

14

Carmustine

  • Alkylating agent
  • Nitrosurea
    • Cross-links DNA
    • Requires bioactivation
    • Crosses BBB → CNS
  • Use: Brain tumors
  • S/E: CNS toxicity

15

Lomustine

  • Alkylating agent
  • Nitrosurea
    • Cross-links DNA
    • Requires bioactivation
    • Crosses BBB → CNS
  • Use: Brain tumors
  • S/E: CNS toxicity

16

Semustine

  • Alkylating agent
  • Nitrosurea
    • Cross-links DNA
    • Requires bioactivation
    • Crosses BBB → CNS
  • Use: Brain tumors
  • S/E: CNS toxicity

17

Streptozocin

  • Alkylating agent
  • Nitrosurea
    • Cross-links DNA
    • Requires bioactivation
    • Crosses BBB → CNS
  • Use: Brain tumors
  • S/E:
    • CNS toxicity
    • Insulin-secreting pancreatic islet tumors

18

Paclitaxel

  • HypERstabilizes polymerized microtubules
    • Mitotic spindle can't break down in M phase → anaphase can't occur
  • Use: Ovarian and breast carcinomas
  • S/E:
    • Neuropathy
    • BM suppression
    • Hypersensitivity

19

Vincristine

  • Vinca alkaloid
    • Binds β-tubulin → inhibits polymerization into microtubules
    • Prevents mitotic spindle formation (M-phase arrest)
  • Use:
    • Solid tumors
    • Leukemias
    • Non-Hodgkin Lymphomas
  • S/E:
    • Peripheral Neuropathy
    • Neurotoxicity
    • Paralytic Ileus
  • Less BM suppression

20

Vinblastine

  • Vinca alkaloid
    • Binds β-tubulin → inhibits polymerization into microtubules
    • Prevents mitotic spindle formation (M-phase arrest)
  • Use:
    • Solid tumors
    • Leukemias
    • Hodgkin Lymphomas
  • S/E: BM suppression (vinblastine blasts BM)

21

Cisplatin

  • Cross-links DNA
  • Use:
    • Testicular carcinoma
    • Bladder carcinoma
    • Ovarian carcinoma
    • Lung carcinoma
  • S/E:
    • Nephrotoxicity
    • Peripheral neuropathy
    • Ototoxicity

22

Carboplatin

  • Cross-links DNA
  • Use:
    • Testicular carcinoma
    • Bladder carcinoma
    • Ovarian carcinoma
    • Lung carcinoma 
  • S/E:
    • Nephrotoxicity
    • Peripheral neuropathy
    • Ototoxicity

23

Etoposide

  • Topoisomerase II inhibitor
    • increases DNA degradation
  • Use:
    • Solid tumors (testicular, small cell lung)
    • Leukemias
    • Lymphomas
  • S/E:
    • BM suppression
    • Alopecia

24

Irinotecan

  • Topoisomerase I inhibitor
    • Prevents DNA unwinding & replication
  • Use: Colon cancer
  • S/E:
    • Severe BM suppression
    • Diarrhea

25

Topotecan

  • Topoisomerase I inhibitor
    • Prevents DNA unwinding & replication
  • Use:
    • Ovarian cancer
    • Small cell lung cancer
  • S/E:
    • Severe BM suppression
    • Diarrhea

26

Hydroxyurea

  • Ribonucleotide reductase inhibitor
    • Decreases DNA synthesis (S-phase)
  • Use:
    • Melanoma
    • CML
    • Sickle cell (increases HbF)
  • S/E: Severe BM suppression

27

Prednisone / Prednisolone

  • Bind intracytoplasmic steroid receptor → alter gene transcription
  • Use:
    • CLL
    • Non-Hodgkin Lymphoma
    • Immunosuppression
  • S/E:
    • Cushing-like symptoms
    • weight gain
    • central obesity
    • muscle breakdown
    • cataracts
    • acne
    • osteoporosis
    • HTN
    • peptic ulcers
    • hypERglycemia
    • psychosis

28

Bevacizumab

  • MAb against VEGF
    • Inhibits angiogenesis
  • Use: Solid tumors (colorectal, renal cell)
  • S/E:
    • Hemorrhage
    • blood clots
    • impaired wound healing

29

Erlotinib

  • EGFR tyrosine kinase inhibitor
  • Use: Non-small cell lung carcinoma
  • S/E: Rash

30

Cetuximab

  • MAb against EGFR
  • Use:
    • Stage IV colorectal cancer (wild-type KRAS)
    • Head & neck cancer
  • S/E:
    • Rash
    • elevated LFTs
    • diarrhea

31

Imatinib

  • Tyrosine kinase inhibitor of BCR-ABL and c-kit
  • Use:
    • CML (BCR-ABL - Philly Chrom)
    • GI stromal tumors (c-kit)
  • S/E: Fluid retention

 

32

Rituximab

  • MAb against CD20
  • Use:
    • Non-Hodgkin lymphoma
    • CLL
    • ITP
    • rheumatoid arthritis
  • S/E: increased risk PML (JC virus)

33

Tamoxifen

  • SERM
    • ANTagonist in breast
    • AGonist in bone
  • Use:
    • Breast cancer Rx
  • S/E:
    • Increased risk endometrial cancer
    • Increased risk thromboembolic events

34

Raloxifene

  • SERM
    • ANTagonist in breast
    • AGonist in bone
  • Use:
    • Breast cancer Rx & prevention
    • Osteoporosis
  • S/E: increased risk thromboembolic events
  • NO increased risk endometrial cancer

35

Trastuzumab

  • MAb against HER-2 (c-erbB2), a tyrosine kinase receptor
    • inhibits HER2-initiated cell signaling & Ab-dependent cytotoxicity
  • Use: HER-2 + breast cancer and gastric cancer
  • S/E: Cardiotoxicity

36

Vemurafenib

  • Small molecule inhibitor of V600E-mutated BRAF
  • Use: metastatic melanoma

37

Chemo drugs causing Ototoxicity

Cisplatin/Carboplatin

38

Chemo drugs causing peripheral neuropathy

Vincristine

39

Chemo drugs causing pulmonary fibrosis

  • Bleomycin
  • Busulfan

40

Chemo drugs causing cardiotoxicity

  • Doxorubicin
  • Trastuzumab
  • Adriamycin

41

Chemo drugs causing nephrotoxicity

Cisplatin/Carboplatin

42

Chemo drugs causing hemorrhagic cystitis

CYclophosphamide

43

Chemo drugs causing myelosuppression

  • 5-FU
  • 6-MP
  • Vinblastine
  • Methotrexate

44

Procarbazine

  • Alkylating agent
  • Forms H2O2 free radicals → DNA damage
    • Activated & metabolized in liver
  • Use: Hodgkin lymphoma
  • S/E:
    • Disulfiram-like reactions
    • Leukemia
    • Pulmonary toxicity

45

Mechlorethamine

  • Alkylating agent
    • Prodrug -- nitrogen mustard
  • Use: Hodgkin lymphoma
  • S/E: Skin irritant

46

Chlorambucil

  • Alkylating agent
    • Slow-acting nitrogen mustard
  • Use: CLL (drug of choice)
  • S/E: BM suppression

47

Thiotepa

  • Alkylating agent
  • Use: Ovarian cancer
  • S/E: BM suppression

48

Docetaxel

  • Hyperstabilizes polymerized microtubules
    • Mitotic spindle can't break down in M phase → anaphase can't occur
  • Use: Ovarian and breast carcinomas
  • S/E:
    • Peripheral Neuropathy
    • BM suppression
    • Hypersensitivity

49

Asparaginase

  • Catalyzes asparagine deamination → aspartic acid + ammonia (in blood)
    • Some neoplastic cells have low levels of asparagine synthase → require external source of asparagine
  • Use: Childhood ALL
  • S/E: Acute pancreatitis

50

Sunitinib

  • Tyrosine kinase inhibitor
  • Use: RCC
  • S/E:
    • Rash
    • BM suppression

51

Sorafenib

  • Tyrosine kinase inhibitor
  • Use: RCC
  • S/E:
    • Rash
    • BM suppression

52

Lapatinib

  • Tyrosine kinase inhibitor
  • Use: Metastatic breast cancer
  • S/E:
    • Rash
    • Diarrhea

53

Everolimus

  • Tyrosine kinase inhibitor
  • Use: Metastatic RCC

54

IFNα-2A

  • Use:
    • Hairy-cell leukemia
    • AIDS-related Kaposi sarcoma
    • CML
  • S/E: myopathy

55

IFNα-2B

  • Use:
    • Hairy-cell leukemia
    • AIDS-related Kaposi sarcoma
    • melanoma
    • follicular lymphoma
  • S/E: myopathy

56

Rx chemo-induced vomiting

Ondansetron (5HT3 antagonist)

57

Rx bone marrow suppression

filgrastim, sargromastim (CSFs)

58

Methotrexate rescue

Leucovorin → folinic acid

59

Cyclophosphamide rescue

  • Mesna → sulfhydryl group binds acrolein
  • N-acetylcystine

60

Cisplatin rescue

  • Amifostine → free radical scavenger
  • Chloride (saline) diuresis

61

Anthracycline rescue

Dexrazoxane

62

Chemo agents with less BM suppression

  • Vincristine
  • Cisplatin
  • Bleomycin
  • Asparaginase

63

Chemo agents working on S phase

  • Cytarabine
  • Antimetabolites (AZA, 6-MP, 6-TG, MTX, 5-FU, cytarabine, cladribine)
  • Etoposide, Teniposide (late)

64

Chemo agents working on G2 phase

  • Etoposide, Teniposide (early)
  • Bleomycin

65

Chemo agents working on M phase

Microtubule inhibitors:

  • Vinblastine
  • Vincristine
  • Paclitaxel

66

Chemo agents working on G0 phase

  • Alkylating agents
  • Nitrosureas
  • Cisplatin

67

6-Thioguanine

  • Purine/thiol analog
  • Activated by HGPRT
  • Can be given with allopurinol

68

Adriamycin

  • Free radical formation → DNA breaks
  • S/E:
    • dilated cardiomyopathy
    • cardiac fibrosis
  • Rescue: Dexrazoxane

69

Teniposide

  • Topoisomerase II inhibitor
    • increases DNA degradation
  • Use:
    • Solid tumors (testicular, small cell lung)
    • Leukemias
    • Lymphomas
  • S/E:
    • BM suppression
    • Alopecia

70

Rx Tumor Lysis Syndrome

Allopurinol

71

Allopurinol

Rx Tumor Lysis Syndrome

72

Mesna

  • Sulfhydryl group binds acrolein
  • Cyclophosphamide/Ifosfamide-induced hemorrhagic cystitis rescue

73

Amifostine

  • Free radical scavenger
  • Cisplatin-induced nephrotoxicity rescue

74

Leucovorin

  • Folinic acid
  • Methotrexate-induced BM suppression rescue
  • Enhances cytotoxicity of 5-FU

75

Dexrazoxane

Doxorubicin/anthracycline-induced cardiotoxicity rescue

76

Log-kill hypothesis

Chemotherapeutic agents have first order kinetics (kill a constant fraction of cells)

  • Solid tumors: low growth fraction → respond poorly to chemo
  • Disseminated cancers: high growth fraction → respond well to chemo

77

Antimetabolites

Inhibit nucleotide synthesis in S phase

  • Methotrexate (folic acid - dihydrofolate reductase)
  • Azathioprine (purine)
  • 6-MP (purine)
  • 6-TG (purine)
  • Cladribine (purine)
  • 5-FU (pyrimidine - thymidylate synthase)
  • Cytarabine (pyrimidine)
  • Hydroxyurea (pyrimidine - ribonucleotide reductase)

78

Alkylating agents

Cell Cycle-Nonspecific (G0 Phase) agents that cross-link DNA → interfere w/replication

  • Cisplatin
  • Busulfan
  • Cyclophosphamide
  • Nitrosureas (-mustines + streptozocin)

79

Antitumor antibiotics

Induce DNA damage → decrease replication

  • Bleomycin (free radicals; G2 Phase)
  • Dactinomycin (intercalation)
  • Doxorubicin (free radicals + intercalation)
  • Daunorubicin (free radicals + intercalation)
  • Adriamycin (free radicals + intercalation)

80

Microtubule Inhibitors

Interfere w/cell division in M phase:

  • Vincristine (binds tubulin → MT instability)
  • Vinblastine (binds tubulin → MT instability)
  • Paclitaxel (hypERstabilizes MT)
  • Doclitaxol (hypERstabilizes MT)

81

DNA Replication Inhibitors

  • Etoposide (Topoisomerase II, peripheral)
  • Teniposide (Topoisomerase II, central + peripheral)
  • Tenotecan (Topoisomerase I)
  • Irinotecan (Topoisomerase I)