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Chemotherapy > Cancer III > Flashcards

Cancer III Flashcards

1
Q

What are cell cycle specific drugs?

A

Antimetabolites

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2
Q

What are cell cycle non-specific drugs?

A

Alkylating agents

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3
Q

How do antimetabolites work?

A

Inhibit DNA/RNA synthesis - S-phase specific

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4
Q

What does methotrexate do?

A

Antimetabolite that is structurally related to folic acid and so inhibits dihydrofolate reductase - targets cells in the S phase

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5
Q

What is methotrexate remained as in red blood cells?

A

MTX-polyglutamate compounds

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6
Q

How can the dose of methotrexate be reduced if it is too high?

A

Leucovorin

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7
Q

How are high doses of methotrexate delivered?

A

IV, IM and intrathecally

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8
Q

How does the unchanged drug appear?

A

In the urine

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9
Q

Does methotrexate have poor or good penetration into the CNS?

A

Poor

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10
Q

When is 6-mercaptopurine used?

A

Maintenance remission in acute lymphoblastic leukaemia and inhibits purine biosynthesis. Incorporated into DNA and RNA leading to non-functional molecules

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11
Q

How can resistance to 6-mercaptopurine arise?

A

Lack of HGPRT or increased drug metabolism

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12
Q

What does 6-fluorouracil do?

A

Deplete intracellular nucleotide pools - interferes with production of dTMP which is needed for DNA synthesis and cell growth

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13
Q

What is 6-fluorouracil often given with?

A

MTX

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14
Q

Can 6-fluorourcail cross the BBB?

A

Yes - excreted in the urine along with metabolites

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15
Q

What is gemcitabine an analogue of?

A

Deoxycytidine - metastatic pancreatic cancer

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16
Q

How is gemcitabine administered?

A

IV and deaminated to a non-toxic product

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17
Q

What is a major side effect of gemcitabine?

A

Myelosuppression

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18
Q

What is cytarabine an analogue of?

A

Cytosine arabinose or AraC that is incorporated into DNA and causes chain termination as no nucleotide can then be added onto it

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19
Q

What does dactinomycin do?

A

Intercalates into the major groove of DNA and interfere with transcription and DNA replication

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20
Q

What is dactinomycin used in combination with and why?

A

MTX as resistance is prevalent due to P-glycoprotein

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21
Q

What are the two anthracyclines?

A

Doxorubicin and daunorubicin

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22
Q

What do anthracyclines do?

A

Intercalate with DNA and generate free radicals that break DNA strands - can also interfere with the dan breakage repair system

23
Q

What are anthracyclines used in combination for?

A

Lung, breast and leukaemia

24
Q

Where do metabolites of anthracyclines appear?

A

Bile and urine - poor penetration into the CNS

25
Q

What stage of the cell cycle do anthracyclines target?

A

S phase and G2 phase

26
Q

What do alkylating agents do?

A

Transfer alkyl groups to DNA, are mutagens and target rapidly diving cells

27
Q

What do some alkylating agents need for metabolic transformation?

A

P450

28
Q

What can alkylating agents be used in combination to treat?

A

Solid and lymphatic tumours

Oral and can cross the BBB so can be used in brain cancer therapy

29
Q

What are platinum coordinated complexes?

A

Cisplatin, carboplatin and oxaliplatin

Carboplatin is less toxic than cisplatin

30
Q

What do platinum coordinated complexes do?

A

From intra and inter strand crosslinks and interferes with DNA replication and transcription and therefore it acts in G1 and S phase

31
Q

What is oxiplatin used in?

A

Colorectal cancer

32
Q

What are the two topoisomerase I inhibitors?

A

Topotecan and irinotecan - S phase specific

33
Q

What can topotecan be used against?

A

Metastatic ovarian cancer and lung cancer

34
Q

What can irinotecan be used against?

A

Colorectal and rectal cancer alongside 5_FU & leucovorin

35
Q

What is the active form of irinotecan?

A

SN-38 - metabolised in cancer cells to form the active component

36
Q

How do irinotecan and topotecan work?

A

Prevent ligation following topoisomerase cleavage

Bind to the enzyme-DNA duplex

37
Q

How are topoisomerase I inhibitors administered?

A

Through IV and excreted in urine

38
Q

What is a problem with topotecan?

A

Myelosuppression

39
Q

What are topoisomerase II inhibitors?

A

Daunorubicin and doxorubicin - intercalate into DNA

Etoposide and teniposide - bind to transient cleavable form of enzyme-DNA complex leading to double strand breaks

40
Q

What are telomerase inhibitors?

A

Imetelstat - direct enzyme inhibitors

Modify oligonucleotides

41
Q

When do vinca alkaloids target cells?

A

Mitosis

42
Q

What do taxanes do?

A

Block mitosis in metaphase by binding to tubulin and inhibiting its polymerisation and stability of microtubules
Induce spindle dysfunction

43
Q

When are taxanes active?

A

G2/M phase

44
Q

What are taxanes used to treat?

A

Ovarian cancer and breast cancers as well as non-small cell lung cancer

45
Q

What are the two vinca alkaloids?

A

Vincristine and vinblastine

46
Q

Are vinca alkaloids neurotoxic?

A

Yes

47
Q

Where is telomerase active?

A

Stem cells

48
Q

Where is telomerase inactive?

A

Somatic cells

49
Q

What is Etoposide used in combination with for testicular cancer?

A

Bleomycin & cisplatin

50
Q

What does teniposide treat?

A

Glinomas and neuroblastomas

51
Q

Can alkylating agents be used in brain cancer?

A

Yes - they are oral bioavailable and cross the BBB

52
Q

What does topoisomerase do?

A

Reversible single-stranded breaks in the DNA a duplex which act to relieve torsional strain

53
Q

Where do platinum coordinated complexes metabolites go to?

A

The urine - poor penetration into the CNS

Chemotherapy (18 decks)

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