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Intro to Cancer Chemotherapy
Classes and intro to cancer agents
46
Pharmacology
Graduate
12/15/2010

Additional Pharmacology Flashcards

 


 

Cards

Term
two broad categories of cancer chemotherapy
Definition
cytotoxic agents - nonspecifically inhibit replication; targeted anticancer drugs - inhibit certain proteins
Term
Induction therapy
Definition
produce rapid reduction in tumor cell burden and thereby produce a symptomatic response; ie - acute lymphocytic leukemia
Term
consolidation therapy
Definition
complete or extend initial remission (different drugs than induction)
Term
maintenance therapy
Definition
sustain remission as long as possible; less-frequent/different drugs
Term
cytotoxic antineoplastic drugs
Definition
cell cycle-specific and cell cycle-non specific

non - all DNA alkylating and most DNA intercalating drugs

Specific - Temsirolimus, DNA synthesis inhibitors; Bleomycin, etopside and teniposide; mitotic inhibitors
Term
cyclin processing (order of 4 major cyclins)
Definition
cyclins prevent progression to the next step of the mitotic pathway

A - end of S to end of G2
B - beginning of G2 to Beginning of M
D - G1
E - S to G2
Term
Limitations of cancer chemotherapy
Definition
drug resistance, drug toxicity, inability to surpress metastasis
Term
drug resistance
Definition
p-glycoprotein pump and multidrug-resistance proten - both act to remove drugs from cells preventing their efficacy

MRP - conjugates with glutathione before excretion

topoisomerase mutations; dihydrofolate reductase mutation; antiapoptotic protein expression modulation

increased tumor cell repair
overexpression of target enzymes
Term
drug toxicity
Definition
non-specific replication inhibitors; nausea and vomiting from medulla; bone marrow suppression

alopecia - hair loss
organ toxicity may occur as well

neuro and pulmonary toxicity have not preventative treatment

renal toxicity can be prevented with mannitol and sodium thiosulfate

minimize with BM transplant and hG-CSF
Term
myelosuppression
Definition
bone marrow suppresion - results in leukopenia/thrombocytopenia and anemia
Term
goals of treatment
Definition
cure - 10 years disease free survival
control - prevent progression
palliation - improve symptoms
Term
adjuvant therapy
Definition
to supplement other treatments (surgery)
Term
neoadjuvant therapy
Definition
given prior to surgery to reduce tumor
Term
maintainence chemo
Definition
lower doses - to control the growth and prolong remission
Term
what allows a cell to survive chemo?
Definition
if it is slowly dividing then it is more likely to survive - Tumor growth fraction can determine this
Term
log kill model
Definition
cells die according to a proportion of the total that are present; follows first-order kinetics
Term
cancer treatment scheduling
Definition
21 days apart to allow regrowth of normal tissues
Term
problem with alkylating agents
Definition
are mutagenic and can cause further neoplasms
Term
effects on fetus
Definition
teratogenesis (1st trimester)
Term
antimetabolites (DNA Synth Inhibitors)
Definition
Two types of these cell-cyle specific Drugs:
1. analogues that terminate DNA elongation
2. Attack enzymes that prevent substrate creation for DNA synthesis

folate antagonists;
purine antagonists
pyrimidine antagonists
ribonucleotide reductase inhibitor
Term
folate antagonists
Definition
methotrexate and pemetrexed (acts on several tetrahydrofolate dependent enzymes)
Term
methotrexate
Definition
inh dihydrofolate reductase and therefore decreases tetrahydrofolate and purine/thymidine synthesis

adverse effects - add leucovorin (fully activated folic acid)
Term
purine antagonists
Definition
purine base analogues:
6-mercaptopurine
6-thioguanine

Purine Nucleoside/tide analogues
Cladribine
fludarabine
clofarabine
nelarabine
Term
purine base analogues
Definition
mercaptopurine/thioguanine -
converted to nucleotide form
inhibit IMP converstion to AMP/GMP (enzyme is inosine monophosphate dehydrogenase)

Mercaptopurine - inhibits de novo purine synthesis (glutamine phosphoribosyl pyrophosphate amidotransferase)

allopurinol is frequently administered to cancer patients due to large build up of uric acid metabolites - mercaptopurine is degraded by xanthine oxidase and therefore must be reduced in dosage if allopurinol is administered
Term
purine nucleoside analogues
Definition
Cladribine (Leustatin)
Fludarabine (Fludara)
Clofarabine (Clolar)
Nelarabine (Arranon)

all are halogenated purine nucleoside analogues which are incorporated into nascent DNA causing termination of replication
Term
pyramidine antagonists
Definition
cytarabine and fluoracil
others - floxuridine, capecitabine, gemcitabine
Term
-bine
Definition
purine/pyrimidine analogues
Term
5-fluorouracil
Definition
uracil analobue that is converted to FdUMP which inhibits thymidylate synthase preventing dTMP formation
Term
ribonucleotide reductase inhibitor
Definition
hydroxyurea - prevents conversion from ribonucleotides to deoxyribonucleotides

uses - chronic myelogenous leukemia, ovarian cancer, melanoma
Term
agents that modify DNA structures
Definition
cross-link DNA
-alkylating agents
-platinum compoounds

Intercalate DNA
-antracycline drugs
others
Term
alkylating agents
Definition
must be activated; electrophiles that attack DNA nucleophilic sites and leave alkyl groups (guanine susceptible)
usually bis-alkylate potential = DNA cross-lining == DNA BREAKAGE = DNA cell death

NOTE: all are mutagenic and carcinogenic
cell cycle non-specific
nitrogen mustards
-cyclophosphamide
nitrosourea drugs
others

1) Nitrogen mustards
Mechlorethamine (Mustargen)
Cyclophosphamide and ifosfamide
(Cytoxan and Ifex)
Chlorambucil (Leukeran)
Melphalan (Alkeran)
2) Nitrosourea drugs
Carmustine (BCNU, Carmubris)
Lomustine (CCNU, Belustine)
Streptozocin (Zanosar)
3) Other alkylating drugs
Busulfan (Myleran)
Dacarbazine (DIC, DTIC-Dome)
Temozolomide (Temodal)
Mitomycin (Mutamycin)
Term
cyclophosphamide
Definition
alkylating agent: treat with MESNA if this causes Cystitis (bladder inflammation)
Term
platinum compounds
Definition
(-platin) cross-link DNA; nephrotoxicity is major toxicity; no alkyl group
Cisplatin (Platinol)
Carboplatin (Paraplatin)
Oxaliplatin (Eloxatin)

note: amifostine co-administration limits nephrotoxicity
Term
drugs that intercalate DNA
Definition
1. insert between paired bases causes unwinding
2. inhibits topoisomerase II
3. formation of free radicals

tox
CHF (free radicals cause from doxyrubicin) - reduce with dexrazoxane
Bleomycin = pulmonary fibrosis

1. Anthracycline drugs
Doxorubicin (Adriamycin)
Daunorubicin (Cerubidine)
Idarubicin (Idamycin)
Mitoxantrone (Novantrone)

2. Other DNA intercalating drugs
Bleomycin (Blenoxane)
Dactinomycin (Cosmegen)
Term
topoisomerase inhibitors
Definition
interfere with enzyme function blocking ligation of nicked strands = permenant strands (S phase specific)

1. Camptothecin analogues
(Topoisomerase I inhibitors)
1) Irinotecan (Camptosar)
2) Topotecan (Hycamtin)

2. Epipodophyllotoxins
(Topoisomerase II inhibitors)
1) Etoposide (VePesid)
2) Teniposide (Vumon)

3. Amsacrine
(Topoisomerase II inhibitor)

note: topoisomeras I fixes single stranded and II fixes double stranded DNA
Term
mitotic inhibitors (microtubule)
Definition
Mitosis specific

vinca alkaloids - prevent tubulin polymerization (metaphase)
vincadictive people make society stagnant

taxanes - inhibit depolymerization (anaphase)
Taxes prevent society from falling apart

can cause neurotoxicity (due to microtubule function in neurons)


1. Vinca Alkaloids
1) Vincristine (Oncovin)
2) Vinblastine (Velban)
3) Vinorelbine (Navelbine)
2. Taxanes
1) Paclitaxel (Taxol)
2) Docetaxel (Taxotere)
3) Abraxane
Term
hormones and their antagonists
Definition
breast cancer
estrogen antagonists
aromatase inhibitors

prostate cancer
androgen antagonists
GnRH receptor modulators

Corticosteroids
Term
breast cancer
Definition
hormonal therapy - growth of breast is stimulated by estrogen (affecting cell growth and proliferation)

inhibit estrogen production (aromatase inhibitors)
blockade of receptors (anti-estrogen drugs)
Term
estrogen antagonists
Definition
tamoxifen; toremifene;

leaves produce transcriptionally inactive

Indications: Estrogen receptor-positve BC

may cause endometrial cancer (only 5 years of use), associated with hot flashes and vaginal bleeding
Term
aromatase inhibitor
Definition
decreases circulating estrogen

indications: advanced and metastatic breast cancer in postmenopausal women

well tolerated (hot flashes/vaginal bleeding)

1) Aminoglutethimide (Cytadren)
2) Anastrozole (Arimidex)
3) Letrozole (Femara)
4) Exemestane (Aromasin)
Term
prostate cancer
Definition
prostate cancer stimulated by androgens which are produced under stim from leuteinizing hormone

GnRH inhibitor - inhibits LH release
Androgen angatonist - compete with receptor

adverse effects - impotence, hot flashes
Term
hematologic malignancies
Definition
corticosteriods
prednisone
dexamethasone

inhibit proliferation and cause atrophy of lymphoid tissue

lymphocytic leukemiase
lymphomas
multiple myeloma
Term
tyrosine kinase inhibitors
Definition
block tyrosine kinase enzymatic activity to prevent downstream activation of cell proliferation pathways


Imatinib (Gleevec)
Dasatinib (Sprycel)
Nilotinib (Tasigna)
Sunitinib (Sutent)
Sorafenib (Nexavar)
Gefitinib (Iressa)
Erlotinib (Tarceva)
Lapatinib (Tykerb)
Term
imatnib
Definition
tyrosine kinase inhibitors; chronic myelogenous leukemia is targed with this drug
Term
targeted anticancer drugs
Definition
Monoclonal antibodies
hematologic malignancies overproduce cell-surface markers
solid tumors over produce growth factor receptors
antibodies against both
less toxic

Rituximab (Rituxan)
Alemtuzumab (Campath)
Gemtuzumab -ozogamicin (Mylotarg)
Trastuzumab (Herceptin)
Cetuximab (Erbitux)
Panitumumab (Vectibix)
Bevacizumab (Avastin)
Term
drugs to know
Definition
Antimetabolites:
Methotrexate
6-Mercaptopurine
6-Thioguanine
5-Fluorouracil
Hydroxyurea
Agents that modify DNA structures:
Cyclophosphamide
Cisplatin
Carboplatin
Doxorubicin
Daunorubicin
Bleomycin
Topoisomerase inhibitors:
Irinotecan
Topotecan
Etoposide

Microtubule inhibitors:
Vincristine
Vinblastine
Paclitaxel
Docetaxel
Hormonal agents:
Tamoxifen
Anastrozole
Letrozole
Leuprolide
Goserelin
Prednisone
Targeted anticancer drugs:
Imatinib
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