Pharmacology Test 3 Ch. 54

Front 1

Cancer cell cycle specific agents include:

Back 1

antimetabolites, bleomycin, podophyllin alkaloids, and plant alkaloids

Front 2

Cancer cell cycle nonspecific agents include:

Back 2

alkylating agents, antibiotics, cisplatin, nitrosoureas

Front 3

drugs that reverse MDR (multi-drug resistance) include:

Back 3

verapamil, quinidine, and cyclosporine

Front 4

Mechanism of Action:
Alkylate within DNA at the N7 position of guanine

miscoding through abnormal base-pairing with thymine or in depurination by excision of guanine residues, leading to strand breakage

Back 4

Alkylating agents

Front 5

alkylating agents include:

Back 5

Nitrogen Mustards
Cyclophosphamide

Ethylenimines
Thiotepa

Alkyl Sulfonates
Busulfan

Nitrosoureas
Carmustine

Front 6

Precursor of an alkylating nitrogen mustard antineoplastic

Use: immunosuppressive agent that must be activated in the liver to form the active aldophosphamide.

Back 6

cyclophosphamide (nitrogen mustard)

Front 7

Positional isomer of cyclophosphamide
Use: is active as an alkylating agent and an immunosuppressive agent

Back 7

Ifosfamide (nitrogen mustard)

Front 8

A necrotizing irritant destructive to mucous membranes.

Use:
It was formerly used as a war gas.
The hydrochloride is used as an anti-neoplastic in Hodgkin's disease and lymphomas.

Back 8

Mechlorethamine

Front 9

An alkylating nitrogen mustard that

Use
is used as an anti-neoplastic in the form of the levo isomer - melphalan

Toxicity
the racemic mixture and the dextro isomer are toxic to bone marrow

potential carcinogen

Back 9

Melphalan

Front 10

A nitrogen mustard alkylating agent
Use:
used as anti-neoplastic for chronic lymphocytic leukemia, Hodgkin's disease, and others.

Back 10

Chlorambucil

Front 11

Nitrosoureas include:

Back 11

Carmustine, Lomustine, Semustine, and Streptozocin-naturally occuring sugar containing

Front 12

Common toxicity of alkylating agents include:

Back 12

Bone marrow depression, with leukopenia and thrombocytopenia

Front 13

These drugs can cause hemorrhagic cystitis

Reduced by coadministration with MESNA

Back 13

Cyclophosphamide and Ifosfamide

Front 14

These drugs are ototoxic and nephrotoxic

Nephrotoxicity reduced by chloride diuresis and hydration

Back 14

Cisplatin and Carboplatin

Front 15

Alkylating agent used to treat ovarian cancer

Back 15

Thiotepa

Front 16

Alkylating agent used to treat chronic myeloid leukemia

Back 16

Busulfan:

Front 17

Alkylating agent used to treat brain tumors

Back 17

Nitrosoureas

Front 18

Alkylating agent used to treat insulin secreting islet cell carcinoma of the pancreas

Back 18

Streptozocin

Front 19

Antimetabolites include:

Back 19

Folic Acid Analogs

Purine Analogs

Pyrimidine Analogs

Front 20

Folic acid analogs include:

Back 20

Methotrexate
Trimetrexate
Pemetrexed

Front 21

An essential dietary factor, from which THF cofactors are formed which provide single carbon groups for the synthesis of precursors of DNA and RNA

Is reduced by DHFR

Back 21

Folate

Front 22

MOA: prevents the formation of THF, causing an intracellular deficiency of folate coenzymes and accumulation of the toxic inhibitory substrate, DHF polyglutamate

The one carbon transfer reactions for purine and thymidylate synthesis cease, interrupting DNA and RNA synthesis

Primarily occurs in the enzyme DHFR

Back 22

Methotrexate

Front 23

Ways that cells can become resistant to methotrexate:

Back 23

Decreased drug transport through the reduced folate carrier or folate receptor protein

Decreased formation of cytotoxic MTX polyglutamates

Increased levels of the target enzyme DHFR through gene amplification and other genetic mechanisms

Altered DHFR protein with reduced affinity for MTX

Front 24

Methotrexate is used to treat:

Back 24

psoriasis, RA, Burkitt's and non-Hodgkins lymphomas, cancer of breast, head, neck, ovary, and bladder

Front 25

To treat bone marrow suppression associated with methotrexate you should administer?

To treat nephrotoxicity you should administer?

Back 25

leucovorin (folinic acid)

Sodium Bicarbonate to alkalinize the urine

Front 26

Pemetrexed is used to treat?

Back 26

Mesothelioma

Front 27

Purine antagonist include?

Back 27

6-thiopurines
6-Mercaptopurine
6-Thioguanine

Fludarabine Phosphate

Cladribine

Front 28

Must be metabolized by hypoxantine-guanine phosphoribosyl transferase (HGPRT) to the nucleotide form

This form inhibits numerous enzymes of purine nucleotide interconversion

Back 28

6-Mercaptopurine

6-Thioguanine

Front 29

M.O.A.- phosphorylated intracellularly by deoxycytidine kinase to the triphosphate form

The metabolite inhibits
DNA polymerase
ribonucleotide reductase

Induces apoptosis

Use
non-Hodgkin’s lymphoma
chronic lymphocytic leukemia

Back 29

Fludarabine Phosphate

Front 30

An antineoplastic agent
M.O.A. -phosphorylated by deoxycytidine kinase and is incorporated into DNA

Causes DNA strand breaks

Use
hairy cell leukemia
chronic lymphocytic leukemia
non-Hodgkin’s lymphoma

Back 30

Cladribine

Front 31

Pyrimidine antagonists include:

Back 31

Fluoropyrimidines
Fluorouracil - S-phase
Capecitabine
Deoxycytidines
Cytarabine
Gemcitabine

Front 32

inhibits thymidylate synthase therefore causing depletion of Thymidylate

Incorporated into DNA and inhibits RNA processing

Back 32

5-FU (5-Fluorouracil)

Front 33

Used to treat carcinomas of the breast, GI tract, ovary, cervix, urinary bladder, prostate, pancreas, and oropharyngeal areas

Combined with levamisole for Tx of colon cancer

Back 33

5-FU

Front 34

pyrimidine nucleoside analog
It is activated to 5’ mononucleotide (ara-CMP) by deoxycytidine kinase

Inhibits DNA synthesis

Back 34

Cytarabine

Front 35

AraC is cell-cycle specific agent
It kills cells in the S-phase
Its actions are specific for the S phase of the cell cycle

Back 35

Cytarabine

Front 36

antineoplastic agents that block the reproduction of tumor cells

Back 36

Vinca Alkaloids:Vinblastine, Vincristine, Vinorelbine

Front 37

Antitumor agents acting as topoisomerase inhibitors

Back 37

Camptothecins: Topotecan

Front 38

Binds to the microtubular protein tubulin in a dimeric form

The drug-tubulin complex adds to the forming end of the microtubules to terminate assembly

Depolymerization of the microtubules occurs

Leads to mitotic arrest at metaphase, dissolution of the mitotic spindle, and interference with chromosome segregation

Cell cycle specific (CCS) agents- M phase

Back 38

Vinca Alkaloids

Front 39

Alkaloid esters derived from the Western and European Yew

MOA:
Mitotic “spindle poison” through the enhancement of tubulin polymerization

Note: they affect microtubules

Back 39

Taxanes: Paclitaxel and Docetaxel

Front 40

Paclitaxel is used to treat:

Docetaxel is used to treat:

Back 40

ovarian and advanced breast cancer

advanced breast cancer only

Front 41

These drugs work by binding to DNA causing
1. intercalation between base pairs and (-) of new RNA or DNA
2. cause DNA strand scission
3. interference with cell replication

Back 41

Antibiotics: bleomycin, doxirubicin, mytomycin

Front 42

MOA of ?

High-affinity binding to DNA through intercalation

Block DNA and RNA synthesis

DNA strand scission via effects on Topoisomerase II

Binding to membranes altering fluidity

Generation of the semiquinone free radical and oxygen radicals

Back 42

Anthracylines:Doxorubicin & Daunorubicin

These are antibiotics

These drugs are used to treat: Breast, Endometrium, Ovary, Testicle, Thyroid

Has major clinical activity in many types of cancer.

Front 43

A tricyclic pentaglycosidic antibiotic from Streptomyces strains

Binds to DNA through an antibiotic-Mg2+ complex

Blocks DNA-directed RNA synthesis

Used to treat testicular cancer and hypercalcemia

Back 43

Plicamycin

Front 44

Bioreductive alkylating agent that undergoes metabolic reductive activation through an enzyme-mediated reduction to generate an alkylating agent that cross-links DNA

Useful in hypoxic tumors

Used to treat:Squamous cell carcinoma of the cervix
Adenocarcinomas of the stomach, pancreas, and lung
2nd line in metastatic colon cancer

Back 44

Mitomycin

Front 45

One of the bi- or tri-functional alkylating agents
binds to DNA, which results in single and double strand breaks following free radical formation and inhibition of DNA synthesis

Cell cycle specific G2 phase

Used for: Testicular cancer
Squamous cell carcinomas of the head and neck, cervix, skin, penis, and rectum

Lymphomas

Intracavitary therapy in ovarian and breast cancers

Back 45

Bleomycin