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Cytotoxic Drugs Flashcards

1
Q

What are the different parts of the cell cycle?

A

G0 to G1
G1 to S
S to G2 (DNA synthesis)
G2 to M

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2
Q

What are the general characteristics of cell cycle specific chemo agents?

A

Tumour specific

Duration of exposure more important than dose

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3
Q

What are examples of cell cycle specific chemo agents?

A

Antimetabolites; impairs nucleotide synthesis/ incorporation
Mitotic spindle inhibitors

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4
Q

What are examples of antimetabolites?

A 
Methotrexate:
Inhibits dihydrofolate reductase
6-Mercaptopurine/ cytosine arabinoside:
Incorporated into DNA
Hydroxyurea:
Impaired deoxynucleotide synthesis
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5
Q

What are examples of mitotic spindle inhibitors?

A

Vinca alkaloids; vincristine/ vinblastine

Taxotere (taxol)

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6
Q

What are the general characteristics of non-cell cycle specific agents?

A

Non-tumour specific; damage normal stem cells

Cumulative dose more important than duration

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7
Q

What are examples of non-cell specific agents?

A

Alkylating agents
Platinum derivatives
Cytotoxic antibiotics

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8
Q

What are examples of alkylating agents?

A

Chlorambucil/ melphalan

Bind covalently to bases of DNA and produce DNA strand breaks by free radical production

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9
Q

What are examples of platinum derivatives?

A

Cisplatin

Carboplatin

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10
Q

What are examples of cytotoxic antibiotics?

A

Anthracyclines; daunorubicin/ doxorubicin/ idarubicin

DNA intercalculation, impair RNA transcription, form free radicals via strand breaks in DNA

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11
Q

What are the immediate side effects to cytotoxic drugs?

A

Bone marrow suppression
Gut mucosal damage
Alopecia

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12
Q

What are examples of drug specific side effects?

A

Vinca alkaloids; neuropathy
Anthracyclines; cardiotoxicity
Cisplatin; nephrotoxicity

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13
Q

What are some specific side effects to alkylating agents?

A

Infertility

Secondary malignancy

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14
Q

What is the basis of combo chemo administration?

A

Non-cross resistant drug combos
Non-overlapping toxicity spectra
Additive/ synergistic mechanisms of action

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15
Q

Why will chemo fail?

A

Slow tumour doubling time

Drug resistant mechanisms

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16
Q

What are some common drug resistant mechanisms that cancers will adopt?

A

Decreased drug accumulation; MDR-1
Altered drug metabolism; cyclophosphamide
Increased DNA repair; cisplatin
Altered gene expression; reduced topoisomerase 2

17
Q

What limited intensive chemo?

A

Myelosuppression

18
Q

What can be done to overcome the myelosuppression associated with intensive chemo?

A

Haematopoietic growth factors
Combine myelosuppressive/ non-myelosuppressive agents
Intensify doses of active drugs (log-linear tumour kill) + stem cell rescue

19
Q

What are sources of stem cells for transplantation?

A

Blood vs bone marrow
Autologous
Allogeneic - sibling or unrelated

20
Q

What are the basic steps for stem cell transplantation?

A

Myeloablative therapy
Stem cell reinfusion
Bone marrow regeneration

21
Q

What is the specific treatment used for CML?

A

Targeted therapy with tyrosine kinase inhibitors

22
Q

What occurs in the G1 phase of the cell cycle?

A

Cell increases in size

Cellular contents duplicate

23
Q

What occurs in the S phase of the cell cycle?

A

DNA replication

24
Q

What occurs in the G2 phase of the cell cycle?

A

Cell prepares for division

25
Q

What occurs in the M phase of the cell cycle?

A

Mitosis followed by cytokinesis

Formation of 2 identical daughter cells

26
Q

What are the phases in the M cycle?

A 
Prophase
Metaphase
Anaphase
Telophase
Cytokinesis
27
Q

What occurs in prophase?

A

Nucleolus disintegrates
Nuclear membrane breaks down
Spindle fibres appear

28
Q

What occurs in metaphase?

A

Chromosomes align at the metaphase plate

29
Q

What occurs in anaphase?

A

Centromeres divide

Sistem chromatids move to opposite poles

30
Q

What occurs in telophase?

A

Nuclear membrane reforms
Chromosomes decondense
Spindle fibres disappear

31
Q

What regulates the cell cycle?

A

Checkpoints

32
Q

What checkpoint is located at G1?

A

Restriction point (R)

33
Q

What will activation of the checkpoint result in?

A

Increased p53 production

p53 is a tumour suppressor gene that stops the cell cycle and starts repair mechanisms for damaged DNA

34
Q

What is the function of Rb in the cell cycle?

A

Restricts the ability of a cell to progress from G1 to S

CDK (cyclin dependent kinase) will phosphorylate it making it unable to restrict cell proliferation

35
Q

What cyclin is present at the G2 checkpoint?

A

Cyclin B

CDK 1

36
Q

What cyclin is present at the start of G1?

A

Cyclin D

CDK4

37
Q

What cyclin is present at the end of G1?

A

Cyclin E

CDK 2

38
Q

What cyclin in present in S?

A

Cyclin A

CDK2

Haematology (31 decks)

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