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Pharmacology II - Exam 3 > Chemotherapy Drugs > Flashcards

Flashcards in Chemotherapy Drugs Deck (44):
1

What are the two classes of alkylating agent?

Nitrogen Mustards
Platinum Analogs

(Also: nitrosoureas and alkylsulfonates, but these weren't discussed)

2

MOA of Alkylating Agents?

Alkylate DNA at N7 position of guanine...leads to protein miscoding and apoptosis

Can also cause cross-linking of DNA...damaged DNA cannot repair and undergoes apoptosis

3

Clinical indications of Cyclophosphamide

Lymphomas
Leukemias
Multiple Myeloma
Breast and Ovarian Carcinoma
Small Cell Lung Cancer
Some Autoimmune Conditions

4

What prevents hemorrhagic cystitis that is a side effect of cyclophosphamide?

MESNA: mecaptoethane sulfonate

5

Clinical Indications of Cisplatin

Testicular, Ovarian, Bladder, Non-Small and Small Cell Lung Cancers

6

Cisplatin has prominent activity during which phase of the cell cycle?

S phase

7

Toxicities of Cisplatin

-Dose-limiting toxicity is cumulateive, leading to irreversible damage to the renal tubules (prevented with mannitol)
-Ototoxic with tinnitus, hearing loss

8

Resistance of Alkylating Agents

-Increased DNA repair ability of the tumor cells
-Decreased transport of alkylating drug into cell
-Increased production of glutathione and glutathione-associated proteins
-Increased glutathione S-transferase activity

9

What are the three subclasses of antimetabolites?

Folic Acid Analogs
Purine Analogs
Pyrimidine Analogs

10

How does Methotrexate work?

Folic acid analog that binds to the active site of DHFR

Blocks the formation of THF, resulting in interruption in DNA, RNA, and protein synthesis

11

Renal excretion of MTX is inhibited when it interacts with...

Penicillin
Cephalosporins
NSAIDs

12

What drug is used in combo with MTX as a rescue drug?

Leucovorin: rescues normal cells from toxicity

13

6-MP and 6-TG are metabolized by ____ to active metabolites ____ and ____

HGPRT
TIMP
TGMP

14

Clinical Uses of 6-MP and 6-TG

6-MP: ALL, AML, Crohn's
6-TG: AML

15

The purpose of allopurinol with 6-MP use

Prevents hyperuricemia by inhibiting 6-MP metabolism by xanthine oxidace

16

Mechanism of Action of 5-FU

5-FU gets converted to 5-FUTP, 5-FdUMP, 5-FdUTP

5-FUMP --> RNA damage
5-FdUMP --> DNA damage and inhibits thymidylate synthase

17

Uses for 5-FU

Colon cancer (5-FdUMP), breast, gastroesophageal, hepatocellular, pancreatic cancer

18

MOA of vinca alkaloids

Binds to B-tubulin and prevents polymerization

Depolymerization of microtubules blocking mitotic spindle formation during M phase

Mitotic arrest at metaphase interferes with chromosome segregation

19

Vinblastine: Indications

Hodgkin's, non-Hodgkin's
Breast Cancer
Testicular Tumors

20

Vinblastine Toxicity

Bone marrow suppression, anorexia, N/V/D, alopecia

21

Vincristine: Indications

Childhood Cancer, Childhood Tumors

22

Vincristine: Toxicities

Peripheral neuritis/neuropathy with paresthesia, muscle weakness

MARROW SPARING

23

Etoposide, Teniposide: Indications

Testicular, Non-small and small cell lung carcinomas, AML, ALL, Hodgkin's and non-Hodgkin's

24

Etoposide, Teniposide: MOA

Blocks tumor cells in the late S-G2 phase of cell cycle through inhibition of topoisomerase II

25

Topotecan and Irinotecan: Indications

Topotecan: Ovarian and small cell lung cancers

Irinotecan: metastatic colon cancer

26

Camptothecins: MOA

Inhibit topoisomerase I resulting in DNA strand breakage

27

Doxorubicine: Indications

Hodgkin's and non-Hodgkin's, breast, ovarian, bladder cancers, ALL

28

Doxorubicin is derived from...

Streptomyces

29

Doxorubicine: MOA

Intercalation interferes with DNA synthesis
Inhibits topoisomerase II leading to DNA fragmentation

30

Doxorubicine: Toxicities

Reversible acute arrhythmias and conduction abnormalities

31

Bleomycin: Toxicities

Dose-limiting pulmonary fibrosis that can be fatal

32

Bleomycin: Indications

Testicular, squamous cell carcinoma, Hodgkin's and non-Hodgkin's

33

Bleomycin: MOA

Intercalation, scission, and fragmentation of DNA due to an oxidation reaction mediated by a DNA-bleomycin-Fe complex

34

Cancer Treatment Modalities

Surgery
Radiotherapy
Chemotherapy
Endocrine Therapy
MAB/Biologics
Small Molecule Inhibitors

35

Log-Kill Hypothesis

Killing action of CCS (cell-cycle specific) drugs follows first order kinetics (a given dose kills a proportion of a cancer cell population

36

Most solid tumors display what type of pattern?

Gompertzian...growth rates decline as tumor expands

37

Dose-limiting toxicity

Each cytotoxic drug is associated with a particular organ that effectively limits the max dose of the drug that can be given to a patient

38

Types of Drug Resistance

1. Primary: tumor cells don't respond to initial chemotherapy
2. Acquired: develops as a consequence of chemotherapy

39

Examples of Drug Resistance

1. Up-regulation of drug resistance transporters
2. Down-regulation of methotrexate transporter
3. Increased expression of DNA repaired enzymes
4. Increased expression enzymes that produce trapping metabolites within resistant cells

40

CSC Theory to Resistance

Anti-cancer treatments can often shrink tumor size by targeting bulk but they fail to target and kill CSCs leading to treatment failure, relapse, and death

41

Properties of CSCs

Undergo asymmetric cell division: 1 CSC and 1 daughter cell
Resistant to standard chemotherapy
Resistant to radiation (linked to loss of suppressor gene p53)

42

Principles of Combination Chemotherapy Regimen

1. Drugs with different mechanism of action should be combined

2. Drugs targeting different populations of cancer cells should be combined CCS with CCNS drugs

3. Drugs with different organ toxicities should be combined, so full/nearly full therapeutic doses can be utilized for each drug

4. Drugs associated with different modes of resistance should be combined to minimize cross-resistance

5. Identify drug combinations that allow for the shortest possible treatment-free period

43

Rapidly growing tumors are most sensitive to...

CCS chemotherapeutic drugs

44

CCNS definition

Cell Cycle Non-Specific Drugs
Drugs capable of exerting their actions on cancer cells that are cycling or in the resting state