Exam 3: Antineoplastic agents Flashcards Preview

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Flashcards in Exam 3: Antineoplastic agents Deck (53):
1

Define Cancer:

A disease of cell proliferation where normal cells are transformed by genetic mutation into cells with dysregulated growth.

2

What are the 3 steps of Carcinogenesis:

1. Transformation
2. Proliferation
3. Metastasis

3

Define the transformation step of carcinogenesis:

- A cell with normal growth changes into a cell with dysregulated growth (Malignancy)
- Genetic Damage
○ Inherited
○ Mutations that alter growth and repair
○ Alterations in or loss of regulatory proteins

4

Define the Proliferation phase of Carcinogenesis

- Growth of transformed cells into a tumor
- Increase in the number of cells

5

Most antineoplastic drugs target what activity?

Target dividing cells

6

Which cells respond best to chemotherapy?

- Small, rapidly dividing cells respond best
- Normal cells also rapidly divided and are also subjected to effects of chemo

7

Define Dose-limiting toxicity

The dosage being administered is limited because of the possibility of causing toxicity

8

What is the challenge of chemotherapy?

To give an adequate dose to kill the cancer cells without killing too many healthy cells

9

Define the Metastasis phase of Carcinogenesis

- Cancer cells acquire the ability to invade tissues throughout the body
- Tumor cells mutate which allows them to invade into tissues and vessels, body cavities, etc. and grow in a new location.

10

What must be taken into consideration before administering chemotherapy to a patient with metastatic lesions?

- As these cells gain mutations, their response to chemotherapy may change. (altered receptors)
- The original tumor may respond well to chemotherapy, but metastatic lesions may be less response = poor prognosis

11

Most chemotherapy agents interfere with what carcinogenesis phase?

Cell proliferation

12

When are cancer cells most sensitive to chemotherapy drugs?

- When the cells are actively going through the cell cycle
- Metabolically active cells are more susceptible to drugs that interfere with cell growth and division

13

What is the tumor suppressor gene that senses DNA damage and arrests the cell cycle?

- p53
This allows time for the damage to be repaired

14

If a cell fails to repair damage due to chemotherapy, what occurs?

- The cell dies by a biochemically-driven programmed cell death
**apoptosis

15

What is the action of p53?

- Helps to suppress cancer; anti-cancer mechanisms.
- Activate DNA repair proteins
- Hold cell cycle at G1/S regulation point so that DNA repair proteins will fix damage, then cell allowed to continue cell cycle.
- Can initiate apoptosis if damage is irreparable
- Induce growth arrest.

16

What things might induce p53?

1. UV radiation
2. Oncogenes
3. DNA damaging drugs

17

What occurs if p53 gene is damaged?

Tumor suppression is severely reduced.

18

Which type of cells are "highly responsive to chemotherapy"?

- Cancer cells that express p53
*includes leukemias, lymphomas, testicular cancer

19

Which cells are minimally responsive or resistant to DNA-damaging chemotherapy drugs?

- Cancer cells that acquire a mutation in p53
*include pancreatic, lung and liver cancers

20

T or F, Every malignant cell MUST be destroyed to "cure" the cancer

True, a single malignant cell can expand clonally to give rise to a tumor.

21

When administering chemotherapy, is there a specific dosage or cycle number that all therapies follow?

Multiple cycles of chemotherapy must be given at the HIGHEST tolerable dose with the most frequent tolerable interval to achieve a cure

22

Chemotherapy is under what order of kinetics?

- First-order kinetics
A constant fraction of tumor cells is killed with each cycle of chemotherapy

23

Which type of tumors do not respond well to chemotherapy?

- Solid tumors
Slower growth/division of these cells

24

Solid tumors often require what type of treatment?

Often require radiation and/or surgery as well as chemotherapy.
- Resistance to chemotherapy drugs often develops!
- Justification for using combination drug therapy

25

Explain Combination Chemotherapy

(B) Includes drugs that act on different molecular targets, at different phases of the cell cycle and with different dose-limiting toxicities.

26

Explain the benefits to Combination Chemotherapy

- This reduces the emergence of drug resistance
- Allows each individual drug to be given at its highest tolerable dose.
- (B) Some regimens offer SYNGERGISTIC BENEFITS
- (B) Typically use intermittent dosing

27

Examples of cancers that require combination chemotherapy

- Hodgkin's disease
- Testicular cancer
- Breast cancer
- Ovarian cancer
- Cervical cancer
- Bladder cancer
- Lung cancer
- Cancer of head and neck

28

The current emphasis in cancer treatment is use of what therapy? Why?

- Drug Combination therapy
- It takes into account phase of the cell cycle
- Potential synergistic action
- Increases efficacy
- Decreases cell resistance

29

Define Cell-Cycle specific drugs

Drugs that affects one phase

30

Define Cell-Cycle non-specific drugs

Drug affects any/all phases

31

T or F, Drugs for chemotherapy are safe for humans to consume (B)

- False, they are not safe.
(B) They lack specificity. They affect malignant cells as well as rapid but normally proliferating cells

32

Name some examples of normal proliferating cells that chemotherapy drugs also attack

Bone marrow, Skin & intestinal mucosa

33

(B)What are the signs of toxicity that appear in the normal cell proliferating areas that are attacked by chemo drugs

- Blood dyscrasias
- Ulcerations of oral mucosa and other sites in GI tract
- Nausea/vomiting

34

(B)Mechanism of Alkylating agents

- (B)Transfer alkyl groups to important cell constituents with amino-, sulfhydryl-, carboxyl-, and phosphate- groups
- (B)Alkylate DNA, probably at guanine as the primary mechanism for cell death
- (B)Interfere with DNA, RNA and proteins to prevent cell metabolism and division

35

What is the primary mechanism for cell death

Alkylate DNA, probably at guanine

36

Name the major classes of Alkylating agents

1. Nitrogen mustards
2. Alkyl sulfonates
3. Ethylenimines
4. Triazines
5. Nitrosureas

37

T or F, Susceptibility to infection is common outcome of treatment with alkylating agents

- True
They are mutagenic, teratogenic, oncolytic, myelosuppressive, immunosuppressive and carcinogenic.

38

Name the 3 given examples of Alkylating agents

1. Cyclophosphamide (Cytoxan)
a. Multiple cancers, bone marrow transplants
2. Ifosfamide (Ifex) = nitrogen mustard
a. Multiple cancers
3. Procarbazine (Matulane)
a. Hodgkin's disease

39

Role of Antimetabolites

- Serve as fraudulent substrates for biochemical interactions
- Interfere with growth of rapidly proliferating cells

40

Are Antimetabolites cycle specific or non-specific?

- Specific
- (B) S phase specific

41

Name the classes of Antimetabolites

- Folic acid antagonists
- Purine antagonists
- Pyrimidine antagonists

42

Action of Folic acid antagonists

1. (B) Inhibits DNA synthesis
2. Inhibit nucleic acid synthesis by blocking the enzyme dihydrofolate reductase

43

Name the Folic acid antagonist drug

- (B) Methotrexate (Rheumatrex, Trexall)
- Used for many cancers; autoimmune diseases

44

Is methotrexate cell cycle specific or non-specific?

- (B) Cell-cycle specific
**S phase

45

Role of Purine antagonists

Inhibit enzymes that convert hypoxanthine ribonucleotide to adenine and xanthine ribonucleotide

46

Name the purine antagonist drug name

- (B) Mercaptopurine (purinethol)
- Lymphoblastic leukemia

47

Function of mercaptopurine

Inhibits DNA and RNA synthesis

48

Is mercaptopurine cell-cycle specific or non-specific

- (B) Cell-cycle specific
**S phase

49

Role of Pyrimidine antagonists

Inhibit pyrimidine synthesis

50

Name the 2 drugs in the pyrimidine antagonist class

1. (B) Fluorouracil (Adrucil) = "5-FU"
2. (B) Cytarabine (Cytosar-U) = "Ara-C"

51

Function of fluorouracil

- Interferes with DNA synthesis or becomes incorporated into RNA
- Many cancers

52

Function of cytarabine

Inhibition of DNA synthesis and repair

53

Are Pyrimidine antagonists cell-cycle specific or non-specific?

- (B) Specific
**S phase