Exam III Antineoplastic Flashcards Preview

Pharm. II > Exam III Antineoplastic > Flashcards

Flashcards in Exam III Antineoplastic Deck (68):
1

What is cancer?

Cancer is a disease of cell proliferation where normal cells are transformed by genetic mutation into cells with dysregulated growth

2

Carcinogenesis occurs in what 3 main steps:?

1) transformation
2) proliferation
3) metastasis

3

What is transformation?

when a cell with normal growth changes into a cell with dysregualted growth (malignancy)

4

What is genetic damage?

-inherited
-gene mutations that alter growth and repair
-alterations in or loss of regulatory proteins

5

What is proliferation ?

-Growth of transformed cells into a tumor
-Increase in the number of cells
-Dividing cells progress through a cell cycle with several phases
-MOST ANTINEOPLASTIC DRUGS TARGET DIVIDING CELLS
-SMALL RAPIDLY DIVIDING CELLS RESPOND BEST TO CHEMO
-NORMAL CELLS ALSO RAPIDLY DIVIDE, are also subjected to effects of chemo.
-RESULT: DOSE LIMITING TOXICITIES


6

What does the critical cell cycle events include ?

The synthesis of DNA (S phase) and the division of the parent cell into 2 daughter cells (M phase= mitosis)

7

Metastasis:
Cancer cells acquire the ability to ____ tissues throughout the body.
Tumor cells _______ which allows them to ______ into tissues and vessels, body cavities, spread thru lymph or blood, and _______ in a _______ location.
**As they gain mutations, their response to chemotherapy may __________ (altered receptors)
Original tumor may respond well to chemo, but _________ may be _____ responsive= ____ prognosis

invade
mutate
invade
grow
new
change
metastatic lesions
less
poor


8

Chemotherapy - Mechanism of Action:
Most chemo agents interfere with _________
_________ selectivity against cancer cells.
**Caner cells are MOST _________ to these drugs when the cells are actively going through the cell _______.
Metabolically active cells are MORE _____ to drugs that interfere with cell ________ and _______.
Chemo is ____ to many cells, but some are able to _______.
DNA damage is sensed by molecules that _______ the cell cycle to allow time for the damage to be repaired by ________.
If damage is not repaired, the cell ______ by a biochemically-driven programmed cell death = _____________

cell proliferation
relative
sensitive
cell
susceptible
growth
division
toxic
recover
arrest
p53
dies
apoptosis

9

What is p53?

-Transcription factor that regulates the cell cycle
-functions as TUMOR SUPPRESSOR
**HELPS TP SUPRESS CANCER; ANTICANCER MECHANISMS

10

What are the anti-cancer mechanisms of p53?

-Active DNA repair proteins
-hold cell cycle at G1/S regulation so that DNA repair will fix damage then cell allowed to continue cell cycle
-can initiate apoptosis is damage is irreparable
-induce growth arrest

11

**p53 is induced after many different _________. Examples include ________, __________, _______

**IF p53 is damaged, tumor suppression is _______________

-stressors
-UV radiation
-oncogenes
-DNA damaging drugs
-reduced

12

Chemotherapy - Mechanism of Action:

A cancer cell that has a defective capability for DNA repair will undergo _________
**Cancer that EXPRESS p53 (leukemias, lymphomas, testicular cancer)= HIGHLY responsive to ______________.
Cancers that acquire a mutation in _______ are minimally responsive or resistant to __________
(pancreatic, lung, and liver cancers)

apoptosis
chemotherapy
p53
DNA damaging chemo drugs

13

Chemotherapy - Mechanism of Action:

A single malignant cell can expand _____to give rise to a ______.
Every malignant cell must be destroyed to _______cancer.
**MULTIPLE CYCELS OF CHEMO MUST BE DONE AT HIGHEST ___________DOSE with frequent tolerable interval to achieve a cure.
_____ order kinetics = a constant fraction of tumor cells is _____ with each cycle of chemo

clonally
tumor
cure
TOLERABLE
first
killed

14

How do solid cancers respond to chemo?

***SOLID cancer DO NOT respond well to chemo
-Slower growth/division of these cells
-Often require radiation/surgery as well
-Resistance to chemo drugs!!! (THAT WHY WE USE COMBO DRUG THERAPY)

15

What does Combination Chemo include?

***Drugs that act on different molecular TARGER at DIFFERENT phases of CELL CYCLE and DIFFERENT DOSES LIMITING TOXICITIES

16

Combination chemo reduces the emergence of drug __________.
Allows each individual drug to be given at its _______dose
Some regimes offer _______________
**Typically use _____________ dosing

resistance
highest tolerable
*SYNERGISTIC BENEFITS

17

What are examples of cancers that require COMBO CHEMO?

1) Hodgkin's disease
2) Testicular
3) Breast
4) Ovarian
5) Cervical
6) Bladder
7) Lung
8) Cancer of the head and neck

18

What is some general information about chemo?

-current emphasis is on combo chemo
-takes into account phase of cell cycle
-potential synergistic action
-increases efficacy
-decreases cell resistance

19

What happens in GO of cycle ?

resting phase

20

What happens in G1 of cycle ?

gap phase; occurs after mitosis; genes for replication are activated

21

What happens in S of cycle ?

DNA synthesis

22

What happens in G2 of cycle ?

second gap phase "pre-mitosis"; DNA repair progresses

23

What happens in M of cycle ?

mitosis

24

How can drugs target the cell cycle?

1) Cell-cycle specific (drugs affect 1 phase)
2) Cell-cycle non-specific (drug affects ANY/all phases)

25

What is a low therapeutic index?

-drugs for chemotherapy are NOT SAFE
-LACK of specificity = affect malignant cells as well as rapid but normally proliferating cells
-bone marrow, skin, intestinal mucosa

26

With low therapeutic index, signs of toxicity appear in which areas ?

-blood dyscrasias
-ulcerations of oral mucosa and other sites in GI
-Nausea/vomiting

27

What is the mechanism for Alkylating Agents?

-Transfer ally groups to important cell constituents with amino-sulfhydryl, -carboxyl-, and phosphate groups

-Alkylate DNA, probably at guanine as the primary mechanism for cell death

**interfere with DNA, RNA AND PROTEINS TO PREVENT CELL METABOLISM AND DIVISION

28

What are the major classes of Alkylating Agents?

1) Nitrogen mustards
2) alkyl sulfonates
3) ethylenimines
4) triazines
5) nitrosureas

29

Alkylating Agents:
susceptibility to infection is ______ outcome of tx.
Most agents are mutagenic, _________, ____________, ________, _______

common
teratogenic
oncolytic
myelosuppressive
immunosuppresive
carcinogenic

30

What are the 10 examples of Alkylating Agents?

1) chlorambucil (Leukeran)- leukemai, lymphoma, multiple cancers
2) ****cyclophosphamide (Cytoxan)-multiple, bone transplants
3) estramustine (Emcyt)= postate
4) ****ifosfamide (Ifex) = nitrogen mustand**= multiple,
5) Iomustine (CeeNu)= brain, lymphoma, melanoma, others
6) melphalan (Aleran)= multiply myeloma, ovarian, neuroblastoma, others
7) ***procarbazine (Matulane) = Hodgkin's
8) streptozocin (Zanosar) = pancreatic , Hodgkin's, colorectal
9) temozolomide (Temodar)= astrocytoma, glioblastoma
10) thiotepa (generic only) = bladder, adenocarcinoma, lymphomas, sarcomas

31

Antimetabolites serve as a what?

-fraudulent substrates for biochemical interactions
-interfere with growth of rapidly proliferating cells
-S PHASE SPECIFIC:
Folic acid antagonists
Purine antagonists
Pyrimidine antagonists

32

Describe the Folic acid antagonists

***INHIBTIS DNA SYNTHESIS
-inhibtis n.a synthesis by blocking the enzyme dihydrofolate reductase

***METHOTREXATE ( Rheumatrex, Trexall)
-used for many cancers; autoimmune
***CELL-CYCLE specific = S phase

33

Describe the Purine antagonists

-Inhibit enzymes that convert hypoxanthine ribonucleotide to adenine and xanthine
ribonucleotide

***MERCAPTOPURINE (Purinethol)
lymphoblastic leukemia
-inhibits DNA and RNA synthesis
***CYCLE SPECIFIC --> S PHASE

34

Describe the Pyrimidine antagonists

-Inhibit pyrimidine synthesis
***fluorouracil (Adrucil) " 5-FU" = many cancers
-interferes w/ DNA synthesis or becomes incorporated into RNA
***cytarabine (Cytosar-U) "Ara-C"= blood cancers
-inhibition of DNA synthesis and repair
***CYCLE SPECIFIC --> S PHASE

35

Platinum Complexs:
Platinum ions surround by ______ ions.
***Inhibts _________ and repair
Induces cell death via ______ or ________.

chloride
DNA synthesis
apoptosis
necrosis

36

What are the 3 platinum complexes:

***___________( )= small-cell lung cancer, ovarian cancer, head and neck cancer
***___________( ) = bladder, testicular, ovarian, head and neck cancer
-___________( )= advanced colon and advanced rectal cancer

carboplatin (Paraplatin)

cisplatin (Platinol)

oxaliplatin (Eloxatin)

37

Platinum based chemotherapy is widely used for the treatment of which cancers:

1) Gynecologic
2) Bladder
3) Testicular (metastatic )
4) Lung
5) CNS
6) Head and neck cancers (squamous cell)

38

What are the toxicities caused by Platinum compounds?

1) Myelosuppression
2) Nephrotoxicity
3) Neurotoxicity
4) Ototoxicity
5) Nausea/vomiting

39

Vinca Alkyloids:

-derived from _____________
**inhibit ____________ by interfering with micro tubular proteins involved in the formation of spindles.
**____ and ______ phase cell cycle specific
****2 EXAMPLES of DRUGS:
Treats _______, ____, ______, _____, ____
high incidence of ________
Side effect: _____________

-periwinkle plant (Vinca rosea)
**mitotic division
**M and S phase
**1) vinblastine (Valban )
**2) vincristine (Oncovin)
-Hodgkin's lymphoma, other Lymphomas, Breast, Testicular, Kaposi's sarcoma,
-side effects
- hearing loss (ototoxic)

40

What are hormonal agents?

**They interrupt cells in G phase
**reduction in amount of circulating hormones

41

Give examples of hormonal agents

1) estrogens
2) androgens
3) protestins
4) glucocorticoids
5) tamoxifen

42

What are **estrogens?

= prostate and mammary CA
-ethinyl estradiol (Estinyl, Feminone)

43

What are **androgens?

= mammary CA in premenopausal women
-testosterone proprionate (Testrx)
-fluoxymesterone (Halotestin)

44

What are** progestins?

= renal and endometrial CA
-medroxyprogesterone (Depo-Provera)
-megestrol (Megace)

45

What are **glucocorticoids?

= hematologic; lymphomas; bone metastases; immunosuppression for organ transplantation

*prednisone (Prednisone Intensol, Sterapred)
-Antitumor effect related to inhibition of glucose transport, phosphorylation, or induction of cell death in inmate lymphocytes

46

What is **tamoxifen(Nolvadex)?

= anti estrogen; breast CA tx and prevention
-competitvely binds to estrogen receptors on tumors and other targets
-DECREASES DNA synthesis and inhibits estrogen effects

**G0 &G1 phases

-Cytostatic not cytocidal
-Many adverse effects: uterine cancer, stroke, pulomonary emboli, liver problems, osteoporosis

47

Antibiotics:
-Cytotoxins **bind with ________ to inhibit _____
-Attack cells in what 2 phases?
-Most effective for _____ ___ tumors

DNA
cell division
1) non-cell cycle specific
2) cell cycle specific
-solid mass

48

What are 8 examples of the antibiotic selected agents?

1) **bleomycin (Blenoxane)
2) **doxorubicin (Adriamycin)
3) **daunorubicin citrate (DaunoXome)
4) dactinomycin (Cosmegen)
5) daunorubicin hydrochloride (Cerubidine)
6)mitoxantrone(Novantrone)
7)mitomycin (Mutamycin)
8) **thalidomide (Thalomid)

49

What is **bleomycin (Blenoxane)

-Cell cycle specific (G2, M)
-squamous cell CA, testicular tumor, lymphomas
-Increased risk for pneumonia, pulomonary fibrosis= limit amounts of prolonged oxygen (leads to fibrosis, necrosis of lung)

50

What is **doxorubicin (Adriamycin)

-Inhibits DNA and RNA synthesis; cell cycle specific (S phase)
-Kaposi's sarcoma, advanced breast and ovarian CA

51

What is **daunorubicin citrate (DaunoXome)

= **HIV- associated Kapok's sarcoma

52

What is dactinomycin (Cosmegen)

**Inhibits DNA and RNA synthesis
-binds with DNA and blocks RNA production
-Pediatric tumors, testicular tumors
-Oral mucosal lesions, diarrhea

53

What is daunorubicin hydrochloride (Cerubidine)

**Inhibits DNA and RNA synthesis
-Acute lymphocytic leukemia
-Causes red color to urine

54

What is mitoxantrone(Novantrone)

**Inhibits DNA and RNA synthesis
-affects entire cell cycle

55

What is mitomycin (Mutamycin)

**Inhibits DNA and RNA synthesis
-alkylating antibiotic; cell-cycle nonspecific, although most effective in late G and S phases

56

What is **thalidomide (Thalomid)

-Angiogenesis inhibitor, immunosuppressant, TNF blocking agent
-Multiple mechanisms of action
-Drug from the 1950s for morning sickness sedation = all first generation offspring had major limb defects

****CLASSIC MODEL DRIG FOR TERATOGENESIS

57

What are the Indication for **thalidomide (Thalomid)?

leprosy; investigational for: **Multiple Myeloma, Crohn's disease, graft versus host disease, *AIDS- related aphthous lesions, other (autoimmune disease)

58

What are the systemic effects of Chemotherapy?

1) Suppression of bone marrow (blood dycrasias)
2) GI disturbances
3) Dermatological reactions
4) Hepatotoxicity
5) Neurotoxicity
6) Nephrotoxicity
7) Immune deficiencies
8) Infertility

59

Describe the suppression of bone marrow (blood dycrasias)effects of Chemotherapy?

-Fatigue, immunosuppression, infection susceptibility

60

Describe the GI disturbances effects of Chemotherapy?

-Nausea, vomiting, diarrhea
-dehydration and electrolyte imbalances
-changes in gut flora

61

Describe the Dermatological reaction effects of Chemotherapy?

-skin lesions, ulcerations
-hair loss (alopecia)

62

Describe the Hepatotoxicity effects of Chemotherapy?

-Enzymatic induction or inhibition via P450 enzymes

63

Describe the Neurotoxicity effects of Chemotherapy?

-Paresthesias, reduced gastric motility, alteration in hormone release, hearing/vestibular disorders

64

Describe the Nephrotoxicity effects of Chemotherapy?

-Hyperurecemia from excess cell destruction and byproducts

65

Describe the Immune deficiencies effects of Chemotherapy?

= immunosuppression
-susceptibility to infection, secondary malignancy

66

Describe the sInfertility effects of Chemotherapy?

= inhibition of spermatogenesis and oogenesis

67

What are the oral manifestations of chemo?

-pose **great discomfort to the patient
-interfere w/ eating,d ringing, swallowing, taking and sleeping

-Many conditions = PAINFUL
-concern that complications pose **SECONDARY INFECTION RISK and may dictate need to discontinue tx temporarily
(may alter success of therapy)

68

What are the managements of oral complications?

1) good plaque control
2) pain control = topical anesthetics
3) salivary replacement for xerostomia -artificial saliva for lubrication
4) fluorides due to caries risk
5) antifungals
6) antivirals
7) antimicrobials mouth rinses or dentifrices