Antineoplastic drugs Flashcards
1
Q
Three main clinical setting of chemotherapy?
A
Primary induction treatment, neoadjuvant, adjuvant post surgical treatment
2
Q
Log Kill
A
fixed proportion of cancer cells that are killed
3
Q
What drugs do you use in G1
A
Steroid hormones and Asparaginase
4
Q
What drugs do you use in S phase
A
Antimetabolites: Methotrexate, 5-flurorouracil, 6-Mercaptopurine
5
Q
What drugs do you use in G2
A
Bleomycin and Etoposide
6
Q
What drugs do you use in M phase
A
Vincristine and Paclitaxel
7
Q
What are some alkylating agents?
A
Nitrogen mustards (Cyclophosphamide) and Nitrosoureas (Carmustine(
8
Q
What are some Anthracycline antibiotics?
A
Doxorubicin and Daunorubicin
9
Q
What monoclonal antibodies are used?
A
Rituximab
10
Q
What RTK inhibitors?
A
Imatinib
11
Q
Schedule dependent –duration of exposure for anti-tumor and toxicity
A
Cell-cycle specific (CCS) agents
12
Q
Cumulative dose for anti tumor and toxic results
A
Non-cell cycle specific agents (NCCS)
13
Q
What is myelosuppression associated with?
A
Alkylating agents and anti-metabolites
14
Q
CCS agents, Glucocorticoid types (hormone)
A
Prednisone and dexamethasone
15
Q
Mechanism of Glucocorticoid
A
G1 phase, cell death in lymphoid illness by apoptosis
16
Q
Adverse effects of Glucocorticoid
A
Hyperglycemia, weight gain, body fluid retention, euphoria, depression, confusion
17
Q
When do you use glucocorticoid?
A
Blood cancer (leukemia, lymphoma, myeloma), breat cancer, brain metastasis, spinal cord compresion
18
Q
CCS agents, Gonadal (hormone)
A
Diethylstillbestrol and testosterone
19
Q
Mechanism of Gonadal (hormone)
A
G1, longer term administration, cytostatic
20
Q
Adverse effect of Gonadal (hormone)
A
cholestatic jaundice (androgen), hypercalcemia, uterine bleeding, hypercoagulable state (estrogen)
21
Q
When do you use Gonadal (hormone)
A
breast cancer and prostrate cancer
22
Q
CCS agents, Gonadal (hormone) anatgonist
A
Tamoxifen and flutamide
23
Q
Mechanism of tamoxifen
A
g1, estrogen Receptor blocker –estrogen positive cell growth stopped
24
Q
Mechanism of Flutamide
A
g1, androgen receptor blocker
25
Adverse effects of Gonadal (hormone) anatgonist
hot flashes, fluid retention (tamoxifen), gynecomastia (flutamide)
26
When do you use Gonadal (hormone) anatgonist?
Breast cancer (tamoxifen) and prostrate cancer (flutamide)
27
CCS agents, Gonadotropin-releasing (hormone) analogs
Leuprolide and Goserelin
28
Mechanism of Gonadotropin-releasing (hormone) analogs
g1, decrease FSH and LH if used constantly
29
Adverse effects of Gonadotropin-releasing (hormone) analogs
transient flare of symptoms with bone metastasis
30
When do you use Gonadotropin-releasing (hormone) analogs
prostate cancer
31
CCS agents Aromatase inhibitors (hormone)
Anastrazole
32
Mechanism of Aromatase inhibitors (hormone)
g1, inhibits estrogen and androstenedione formation
33
Adverse effects of Aromatase inhibitors (hormone)
nausea, asthenia, headache, hot flashes
34
When do you use Aromatase inhibitors (hormone)?
advanced breast cancer
35
CCS miscellaneous Antineoplastic agent
L-Asparaginase
36
Mechanism of L-Asparaginase
g1, catalyze Asn to Asp and NH3, decreases serum Asn which is necessary for growth of certain lymphoid cells
37
Adverse effects of L-Asparaginase
hypersensitivity, inhibits protein synth--decrease clotting factors, hypoalbuminemia
38
When do you use L-Asparaginase?
Lymphoid malignancy, Acute lymphoblastic leukemia, T-cell leukemia, T-cell lymphoma (so Lymphocytes issue--specifically T cells)
39
Types of antometabolites used to kill cells in S phase of cell cycle
Methotrexate (MTX), 6-mercaptopurine, cytarabine (Ara-c) and 5-Flurouracil (5-Fu)
40
Mechanism of MTX
S phase, analog of folic acid, inhibit DHFR so decrease A,G,T in cell
41
Adverse effects of MTX
myelosuppression, GI toxicity
42
When do you use MTX
acute leukemia, breast cancer, non-hodgkin's and T-cell lymphomas
43
Mechanism of 6-mercaptopurine
S phase, inhibits purine metabolism after activation of HGPRT , a purine analogue --affect replication, transcription and stability
44
Adverse effects of 6-mercaptopurine
bone marrow suppression
45
When do you use 6-mercaptopurine ?
Acute leukemias (ALL and AML)
46
Mechanism of cytarabine (Ara-c)
S phase, tumor cell kinase activate it to form nucleotide that suppresses pyrimidine metabolism
47
Adverse effects of cytarabine (Ara-c)
bone marrow suppression, N/V, mucositis
48
When do you use cytarabine (Ara-c) ?
in acute leukemias
49
Mechanism of 5-Flurouracil (5-Fu)
S phase, activated to metabolite, inhibits thymidylate synthase--thymine less death of tumors, a pyrimidine analog --affects of DNA/RNA stability, elongation, transcription
50
Adverse effects of 5-Flurouracil (5-Fu)
diarrhea, bone marrow suppression, ulcerative stomatitis
51
When do you use 5-Flurouracil (5-Fu)?
in solid tumors
52
CCS for G2 phase?
Bleomycin (antobiotics) and Etoposide (plant alkaloid, podophyllotoxin)
53
Mechanism for Bleomycin (antobiotics)
G2, glycopeptide mixture alters nucleic acid functions via free radical form
54
Adverse effects of Bleomycin (antobiotics)
bone marrow sparing, pulmonary fibrosis, skin thickening, hypersensitivity reactions
55
When do you use Bleomycin (antobiotics)?
Hodgkin's and other lymphomas, squamous cell and testicular cancers
56
Mechanism for Etoposide (plant alkaloid, podophyllotoxin)
late S/early G2, topoisomerase II inhibitor
57
Adverse effects of Etoposide (plant alkaloid, podophyllotoxin)
Neutropenia, N/V, diarrhea, hepatic dysfunction (high dose)
58
When do you use Etoposide (plant alkaloid, podophyllotoxin)?
Testicular, small cell carcinoma, and prostate cancer
59
CCS-M phase drugs
Vincristine and Vinblastine (Vinca alkaloids) and Paciltaxel (Taxane)
60
Mechanism for Vincristine and Vinblastine (Vinca alkaloids)
M phase, binds tubulin and block mitotic spindle activity--destabilizes microtubule complex --enhance depolymerization
61
Adverse effects of Vincristine and Vinblastine (Vinca alkaloids)
neurotoxic (Vincristine) and bone marrow suppression (Vinblastine)
62
When do you use Vincristine and Vinblastine (Vinca alkaloids)?
Acute leukemias, Hodgkin's and other lymphomas, kaposi's sarcoma, neuroblastoma and testicular cancer
63
Mechanism for Paciltaxel (Taxane)
M phase, block mitotic spindles disassembly, stabilze microtubule ad inhibit depolymerization--opposite of vinca alkaloids but same effect
64
When do we use Paciltaxel (Taxane)?
Advanced breast and ovarian cancer
65
What are some cell cycle non-specific agents
Cisplatin (alkylating agents: platinum coordination compound), Cyclophosphamide (Alkylating agents: Nitrogen mustard), Cartmustine (alkylating agents, non classical, nitrosourea), Procarbazine (Alkylating agents: non classical)
66
Mechanism for Cisplatin (alkylating agents: platinum coordination compound)
CCNS, covalent bonds with DNA, inhibits DNA replication and transcription, miscoding
67
Adverse effects of Cisplatin (alkylating agents: platinum coordination compound)
Bone marrow sparing, peripheral neuropathy, renal insufficiency, N/V
68
When do you use Cisplatin (alkylating agents: platinum coordination compound)?
Bladder cancer, lung, ovaries, testicles
69
Mechanism for Cyclophosphamide (Alkylating agents: Nitrogen mustard)
CCNS, covalently bond with DNA, activated via hepatic cytochrome P-450
70
Adverse effect of Cyclophosphamide (Alkylating agents: Nitrogen mustard)
forms acrolein, causing bladder toxicity
71
When do you use Cyclophosphamide (Alkylating agents: Nitrogen mustard)?
Breast and ovarion cancers; non-hodgkin's lymphoma
72
Mechanism for Cartmustine (alkylating agents, non classical, nitrosourea)
CCNS, highly lipid soluble
73
Adverse effects of Cartmustine (alkylating agents, non classical, nitrosourea),
leukopenia, pulmonary fibrosis, N/V
74
When do you use Cartmustine (alkylating agents, non classical, nitrosourea)?
adjunctively in brain tumors (glioblastoma; lymphoma)
75
Mechanism for Procarbazine (Alkylating agents: non classical)
CCNS, activation by hepatic cyp450 in liver for active metabolites--similar effects on DNA as classic alkylating agents
76
Adverse effects of Procarbazine (Alkylating agents: non classical)
may cause leukemia, bone marrow suppression, N/V
77
When do you use Procarbazine (Alkylating agents: non classical)?
Hodgkin's lymphoma; glioma
78
What are some anthracycline antibiotics used in CCNS
Doxorubicin, Daunorubicin
79
Mechanism for Doxorubicin
CCNS, inhibits topiosomerase II, intercalate with DNA, form free radicals
80
What are the adverse effects of Doxorubicin
Breast, endometrial, lung, and ovarion cancers, Hodgkin's lymphoma
81
When do use Doxorubicin?
Brest, endometerial, lung, and ovarian cancers; Hodgkin's lymphoma
82
Mechanism for Daunorubicin
CCNS, inhibit topiosomerase II , intercalate with DNA, form free radicals
83
What are the adverse effects of Daunorubicin
Myelosuppression, cardiotoxicity is dose-limiting
84
When do you use Daunorubicin?
Leukemias
85
What are other antibiotics used in CCNS
Dantinomycin and mitomycin
86
Mechanism for Dantinomycin
CCNS, inhibits DNA-dependent RNA synthesis
87
What is the adverse effects of Dantinomycin
bone marrow suppression
88
When do you use Dantinomycin?
Choriocarcinoma, Wilm's tumor, rhabdomysocarcoma, testicular, Ewing sarcoma
89
Mechanism of mitomycin
CCNS, biotransformed alkylating agent
90
Adverse effects of mitomycin
Bone marrow suppression
91
When do you use mitomycin
Colon cancer, superficial bladder, stomach, pancreatic cancer
92
Interferon-alpha although no longer used, for test purpose it is used in?
it is used for T-cell lymphoma
93
Miscellaneous Antineoplastic agents
Monoclonal antibodies (Rituximab) and Imatinib
94
Mechanism of Monoclonal antibodies (Rituximab)
interact with CD-20 of normal and malginant B-lymphocytes
95
What is the adverse effect of Monoclonal antibodies (Rituximab)?
myelosuppression, hypersensitivity
96
When do you use Monoclonal antibodies (Rituximab)?
non Hodgkin's lymphoma
97
Mechanism of Imatinib
inhibits abnormal Tyrosine kinase created by philidelphia chromosome in CML
98
What is the adverse effect Imatinib ?
Diarrhea, nausea, cramps, fatigue
99
When do you use Imatinib ?
Philadelphia positive CML
100
Mechanism of Alkylating agent drug resistance
increased DNA repair and formation of trapping agents
101
Mechanism of 5-fluorouracil and 6-mercaptopurine drug resistance
decreased activation of pro-drug
102
Mechanism of Alkylating agent, Dactinomycin, MTX, drug resistance
decreased drug accumulation via increase in transporters
103
Mechanism of Vinca alkaloids, MTX, Etoposide and gonadal hormones drug resistance
change in target enzymes or receptors
104
Mechanism of pyrimidine and purine analogs drug resistance
formation of drug-inactivating enzymes
105
Drug toxicities: Vincristine
Peripheral neuropathy
106
Drug toxicities: Bleomycin
pulmonary fibrosis, fever, blisters, anaphylaxis
107
Drug toxicities: MTX
Myelosuppresion, mucositis, crystalluria
108
Drug toxicities: Cisplatin
nephrotoxicity, acoustic, and peripheral neuropathy
109
Drug toxicities: Doxo-Daunorubicin
cardiomyopathy
110
Drug toxicities: Cyclophosphamide
hemorrhagic cystitis
111
How can multiple anticancer drugs may occur?
increased expression of MDR1 --increase cell surface glycoproteins involved in drug efflux --drive out drug molecules through ATP usage
112
Various drug resistance mechanism:
increased drug efflux, mutation of drug target, DNA damage repair, activation of alternative signalling pathways or evasion of cell death
113
What can drug resistance do to cancer treatments?
limit effectiveness of therapies, amount of drugs that can be administered and limit the amount of drugs that reaches the tumor
