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Pharm 2 - Exam 3 > Lecture 5 - Chemo Drugs > Flashcards

Lecture 5 - Chemo Drugs Flashcards

1
Q

Nitrogen mustards

A

cyclophophamide

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2
Q

Cyclophosphamide

A

nitrogen mustards

indication:
lymphomas, leukemias, breast and ovarian cancers, small cell lung cancer

SE:
dose limiting toxicity myelpsuppression
hemorrhagic cystitis - prevent with MESNA

MOA:
CCNS, bi-functional DNA alkylating agent; alkylates guanine residues; produces interstrand crosslinks

Resistance:
increased DNA repair capacity
decreased transport of alkylating agent into cancer cell
increased glutathione S-transferase activity

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3
Q

What is the clinical application of cyclophosphamide?

A

lymphomas, leukemias, breast and ovarian cancers, small cell lung cancer

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4
Q

What are the SE of cyclophosphamide?

A

dose limiting toxicity myelpsuppression

hemorrhagic cystitis - prevent with MESNA

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5
Q

What is the MOA of cyclophosphamide?

A

CCNS, bi-functional DNA alkylating agent; alkylates guanine residues; produces interstrand crosslinks

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6
Q

What resistance is present in cyclophophamide?

A

increased DNA repair capacity
decreased transport of alkylating agent into cancer cell
increased glutathione S-transferase activity

(this is the same resistance present with platinum analogs like cisplatin)

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7
Q

platinum analogs

A

cisplantin

oxaliplatin

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8
Q

Cisplantin

A

platinum analog

indication:
testicular, ovarian, bladder, non-small cell lung, colon, and small cell lung cancers

SE: dose-limiting toxicity is nephrotoxicity
prevent nephrotoxicity with hydration and mannitol diuresis

MOA:
CCNS, bi-functional DNA alkylating agents; alkylates guanine residues; produces interstrand crosslinks

Resistance:
increased DNA repair capacity
decreased transport of alkylating agent into cancer cell
increased glutathione S-transferase activity

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9
Q

What is the clinical indication for cisplatin?

A

testicular, ovarian, bladder, non-small cell lung, colon, and small cell lung cancers

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10
Q

What is the MOA for cisplatin?

A

CCNS, bi-functional DNA alkylating agents; alkylates guanine residues; produces interstrand crosslinks

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11
Q

What are the SE of cisplatin?

A

dose-limiting toxicity is nephrotoxicity

prevent nephrotoxicity with hydration and mannitol diuresis

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12
Q

Methotrexate

A

antimetabolite cancer drug

indication:
breast, head, neck, bladder, and lung carcinomas; lymphomas, ALL

SE:
dose limiting toxicity myelosuppression

MOA:
CCS, folic acid analog; inhibits DHFR, which prevents formation of THF, a cofactor for thymidylate, purine and amino acid synthesis

Resistance: 
decreased transport via down-regulation of reduced folate carrier protein 
decreased FPGS 
amplification of DHFR
mutation of DHFR
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13
Q

What is indication of Methrotrexate?

A

breast, head, neck, bladder, and lung carcinomas; lymphomas, ALL

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14
Q

What is the MOA of methrotrexate?

A

CCS, folic acid analog; inhibits DHFR, which prevents formation of THF, a cofactor for thymidylate, purine and amino acid synthesis

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15
Q

What are the SE of methrotrexate?

A

dose limiting toxicity myelosuppression

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16
Q

What resistance is present with methotrexate?

A

decreased transport via down-regulation of reduced folate carrier protein
decreased FPGS
amplification of DHFR
mutation of DHFR

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17
Q

5-fluorouracil

A

antimetabolite

indication:
colon, breast, gastroesophageal, hepatocellular, pancreatic carcinomas

SE:
dose limiting toxicity myelosuppression

MOA:
CCS; pyrimidine analog converted to 5FdUMP, which inhibits TS activity

resistance:
amplification of TS gene

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18
Q

What is the indication for 5-florouracil?

A

colon, breast, gastroesophageal, hepatocellular, pancreatic carcinomas

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19
Q

What are the SE of 5-fluorouracil?

A

dose limiting toxicity myelosuppression

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20
Q

What is the MOA of 5-fluorouracil?

A

CCS; pyrimidine analog converted to 5FdUMP, which inhibits TS activity

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21
Q

What resistance is present for 5-fluorouracil?

A

amplification of TS gene

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22
Q

6-mercaptopurine

A

antimetabolite

indication:
ALL and AML

SE:
dose limiting toxicity myelosuppresion

drug interaction between 6-MP and allopurinol leading to life-threatening myelosuppresion

MOA:
CCS; purine analog converted to Thio-dGTP
Thio-dGTP incorporated into DNA of replicating cancer cells, leading to apoptosis

Resistance:
down-regulation of HGPRT activity

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23
Q

What are the indications for 6-mercaptopurine?

A

ALL and AML

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24
Q

What are the SE of 6-mercaptopurine?

A

SE:
dose limiting toxicity myelosuppresion

drug interaction between 6-MP and allopurinol leading to life-threatening myelosuppresion

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25
Q

What is the MOA of 6-mercaptopurine?

A

MOA:
CCS; purine analog converted to Thio-dGTP
Thio-dGTP incorporated into DNA of replicating cancer cells, leading to apoptosis

6MP converted to TIMP by HGPRT
TIMP converted to Thio-dGETP via TPMT

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26
Q

What resistance is present with 6-mercaptopurine?

A

Resistance:

down-regulation of HGPRT activity

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27
Q

Vinca Alkaloids

A

vinblastine

vincristine

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28
Q

Vinblastine

A

and vincristine (vinca alkaloids)

indication:
vinBlastine - Breast cancer, hodgkins and non-hodgkins lymphoma
vinCristine - Childhood leukemias and cancers

SE:
vinBlastine - dose limiting toxicity Bone marrow suppression

vincrsitine - dose limiting toxicitity peripheral neuropathies; *bone marrow sparing

MOA:
CCS; binds to Beta-tubulin and prevents polymerization of microtubules

resistance:
increased MDR1 activity

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29
Q

What are the indications for vinca alkaloids?

A

vinBlastine - Breast cancer, hodgkins and non-hodgkins lymphoma
vinCristine - Childhood leukemias and cancers

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30
Q

What are the SE of vinca alkaloids?

A

SE:
vinBlastine - dose limiting toxicity Bone marrow suppression

vincrsitine - dose limiting toxicitity peripheral neuropathies; *bone marrow sparing

31
Q

What is the MOA of vinca alkaloids?

A

MOA:

CCS; binds to Beta-tubulin and prevents polymerization of microtubules

32
Q

What resistance is present with vinca alkaloids?

A

resistance:

increased MDR1 activity

33
Q

Taxanes

A

paclitaxel and docetaxel

indication:
ovarian, breast, bladder, and non-small cell lung cancers

SE:
dose limiting toxicities include both myelosuppresion and peripheral neuropathies

MOA:
CCS; binds with high affinity to beta-tubulin and stabilizes microtubules (stops depolymerization)

resistance:
increased MDR1 activity

34
Q

What are the indications for taxanes?

A

paclitaxel and docetaxel

indication:
ovarian, breast, bladder, and non-small cell lung cancers

35
Q

What are the SE of taxanes?

A

paclitaxel and docetaxel

SE:
dose limiting toxicities include both myelosuppresion and peripheral neuropathies

36
Q

What is the MOA of taxanes?

A

paclitaxel and docetaxel

MOA:
CCS; binds with high affinity to beta-tubulin and stabilizes microtubules (stops depolymerization)

37
Q

What resistance is present with taxanes?

A

paclitaxel and docetaxel

resistance:
increased MDR1 activity

38
Q

Epipodophyllotoxins

A

etoposide

indication:
testicular cancer, non-small cell and small cell lung carcinoma, AML, ALL, hodgkins and non hodgkins lymphoma

SE:
dose limiting toxicity myelosuppression

MOA:
CCS; inhibits topoisomerase 2

resistance:
increased MDR1 activity

39
Q

Camptothecins

A

irinotecan

indication:
topotecan for ovarian and small cell lung cancers
metastatic colon cancer

SE:
dose limiting toxicity diarrhea and/pr myelosuppression

MOA:
CCS (at higher concentrations -CCNS); inhibits topoisomerase 1

resistance:
increased MDR1

40
Q

What are the indications or Camptothecins?

A

irinotecan

indication:
topotecan for ovarian and small cell lung cancers
metastatic colon cancer

41
Q

What are the SE of Camptothecins?

A

irinotecan
SE:
dose limiting toxicity diarrhea and/pr myelosuppression

42
Q

What is the MOA of Camptothecins?

A

irinotecan
MOA:
CCS (at higher concentrations -CCNS); inhibits topoisomerase 1

43
Q

What resistance is present with Camptothecins?

A

irinotecan
resistance:
increased MDR1

44
Q

Anthracycline antibiotics

A

doxorubicin

45
Q

Doxorubicin

A

anthracycline antibiotics

indications:
hodgkin’s and non hodgkins, breast, ovarian, and bladder cancers, ALL

SE: (CCNS)
dose limiting irreversible chronic cardiomyopathy

MOA:
DNA intercalation that interferes with DNA and RNA synthesis
inhibit topoisomerase 2
free radical formation leading to DNA scission

Resistance:
increased MDR1
increased glutathione peroxidase activity
resistance rendering mutations of topoisomerase 2

46
Q

What is the indication for Doxorubicin?

A

indications:

hodgkin’s and non hodgkins, breast, ovarian, and bladder cancers, ALL

47
Q

What are the SE of Doxorubicin?

A

SE:

dose limiting irreversible chronic cardiomyopathy

48
Q

What is the MOA of Doxorubicin?

A

MOA: (CCNS)
DNA intercalation that interferes with DNA and RNA synthesis
inhibit topoisomerase 2
free radical formation leading to DNA scission

49
Q

What resistance is present with Doxorubicin?

A

Resistance:
increased MDR1
increased glutathione peroxidase activity
resistance rendering mutations of topoisomerase 2

50
Q

Bleomycin

A

indication:
testicular carcinoma, SCC, hodgkins and non hodgkins lymphomas

SE:
dose limiting pulmonary fibrosis that may be fatal

MOA:
CCS; intercalation, scission and fragmentation of DNA due to oxidation by DNA-belomycine-Fe(2) complex

Resistance:
increased levels of bleomycin hydrolase
increased DNA repair activity

51
Q

What are the indications for Bleomycin?

A

indication:

testicular carcinoma, SCC, hodgkins and non hodgkins lymphomas

52
Q

What are the SE of Bleomycin?

A

SE:

dose limiting pulmonary fibrosis that may be fatal

53
Q

What is the MOA of Bleomycin?

A

MOA:

CCS; intercalation, scission and fragmentation of DNA due to oxidation by DNA-belomycine-Fe(2) complex

54
Q

What resistance is present with Bleomycin?

A

Resistance:
increased levels of bleomycin hydrolase
increased DNA repair activity

55
Q

Etoposide

A

epipodophyllotoxin

indication:
testicular cancer, non-small cell and small cell lung carcinoma, AML, ALL, hodgkins and non hodgkins lymphoma

SE:
dose limiting toxicity myelosuppression

MOA:
CCS; inhibits topoisomerase 2

resistance:
increased MDR1 activity

56
Q

What is the indication for etoposide?

A

testicular cancer, non-small cell and small cell lung carcinoma, AML, ALL, hodgkins and non hodgkins lymphoma

57
Q

What is the SE of etoposide?

A

dose limiting toxicity myelosuppression

58
Q

What is the MOA of etoposide?

A

CCS

inhibits topoisomerase 2

59
Q

What resistance is present with etoposide?

A

increase MDR1 activity

60
Q

Which chemo drugs interfere with nucleotide synthesis or degradation?

A

6MP

Methotrexate

61
Q

Which chemo drugs interfere with DNA synthesis?

A

5-FU

Doxorubicin

62
Q

Which chemo drugs damage DNA?

A 
Bleomycin
Doxorubicin
Cisplatin
Cyclophosphamide
Etoposide
63
Q

Which chemo drugs interefer with mitosis?

A

vincristine

vinblastine

64
Q

Chemo drugs used for lymphomas?

A 
methotrexate
Cyclophosphamide
Doxourbicin
Bleomycin
etoposide
vinblastine
65
Q

Chemo drugs used for leukemias?

A 
methotrexate (ALL) 
6MP (ALL, AML) 
Cyclophosphamide
Doxorubicin (ALL) 
Etoposide (AML, ALL) 
Vincristine (ALL)
66
Q

Chemo drugs used for lung cancer?

A 
Methotrexate (both) 
Paclitaxel (non-small) 
Cyclophosphamide (small) 
Cisplatin (both) 
etoposide (both) 
irinotecan (both)
67
Q

Chemo drugs used for breast cancer?

A 
Methorexate (also head and neck) 
Paclitaxel
5FU
cyclophosphamide
Doxorubicin
vinBlastine
68
Q

Chemo drugs used for ovarian cancer?

A 
paclitaxel
cyclophosphamide
cisplatin
doxorubicin
irinotecan
69
Q

Chemo drugs used for colon cancer?

A

5FU
Cisplatin
irinotecan (metastatic)

70
Q

Chemo drugs used for testicular cancer?

A

cisplatin
Bleomycin
etoposide

71
Q

Chemo drugs used for bladder cancer?

A

methotrexate
paclitaxel
Cisplatin
doxorubicin

72
Q

Chemo drugs used for hepatocellular and pancreatic carcinomas?

A

5FU (also colon, breast, gastroesophageal)

73
Q

Chemo drug used for SCC?

A

Bleomycin

Pharm 2 - Exam 3 (6 decks)

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