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Pharm Y2S2 > Cancer > Flashcards

Cancer Flashcards

1
Q

What is the purpose of chemotherapy?

A

Prevent cell growth

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2
Q

How does chemotherapy target DNA?

A
  • indirect interaction with DNA

- prevention of nucleic acid synthesis by inhibiting one or more enzymes involved

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3
Q

Give examples of alkylating agents

A
  • Melphalan
  • Chlorambucil
  • Cyclophosphamide
  • Decarbazine
  • Bulsulfan
  • Temozolamide
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4
Q

How do mustards work?

A

Attack guanine in DNA, this causes cross linking of DAN strand - they can’t open and be copied for cell division.
Linkage inhibits DNA synthesis - has a cytotoxic effect

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5
Q

Which other cells are also affected by mustards?

A

Those that divide frequently - GIT, bone marrow, testicles and ovaries

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6
Q

What is the state of the nitrogen on chlorambucil?

A

nitrogen lone pair is delocalised

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7
Q

What does melphalan mimic?

A

An amino acid - drug enters by phenylalanine amino acid transporter

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8
Q

What is mitomycin C?

A

a pro-drug that requires reductive activation.

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9
Q

What do alkylating agents contain?

A

Highly electrophilic groups

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10
Q

How do alkylating agents work?

A

They form covalent bonds to nucleophilic groups in DNA. They prevent replication and transcription

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11
Q

What can alkylation of nucleic acid bases lead to?

A

Mutations which are carcinogenic

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12
Q

What is platinum covalently linked to in cis-platen?

A

Chloro-substituents

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13
Q

Where are chemotherapeutic metal complexes activated?

A

In cells with low Cl- ion conc

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14
Q

How does cisplatin work?

A

Binds to DNA regions rich with guanine units forming intra-strand links

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15
Q

What are the toxic side effects of cisplatin?

A
  • severe nausea and vomiting
  • nephrotoxicity
  • ototoxicity
  • bone marrow suppression
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16
Q

What do hydration procedures do?

A

Reduce side effects making it harder for drugs to activated in non-cancer cells

17
Q

What is given as anti-sickness medication?

A

Metoclopramide

18
Q

Give an example of an intercalating agent.

A

Doxorubicin

19
Q

How do intercalating agents work?

A

Slide between stacked bases inserted between adjacent pairs - they are stabilised by electrostatic interactions between DNA phosphate groups and positively charged amino group of sugar moiety. This leads to inhibition of topo II and also generates O2 free radicals

20
Q

What are the side effects of intercalating agents?

A
  • nausea & vomiting
  • myelosuppresion
  • alopecia
  • cardiotoxicity
21
Q

How do DNA topoisomerases work?

A

They modify the topological state of DNA by inducing transient single strand or double strand - this leads to DNA breakage. This is essential for uncoiling of DNA for replication, transcription or recombination

22
Q

What do inhibitors of DNA topoisomerases do?

A

Block the action of topoisomerase leading to permanent single strand or double strand break

23
Q

How does Etopside work?

A

It forms a tertiary complex with DNA and topoisomerase II, this prevents DNA re-ligation so the double strand breaks. It is effective in chemo-sensitive tumours.

24
Q

How do antimetabolites work?

A
  • They interfere with production of nucleic acids.
  • Inhibit production of deoxyribonucleoside triphosphate, precursors of DNA synthesis
  • inhibit formation of normal precursors by completing for metabolic enzymes
25
Q

Give examples of antimetabolites.

A

5-FU
Methotrexate
Gemcitabine

26
Q

What are vincristine and vinblastine used to treat?

A

Leukaemia and Hodgkins lymphoma

27
Q

How do vincristine and vinblastine work?

A

They prevent polymerisation of microtubules

28
Q

What is taxol used to treat?

A

Lung, ovarian and breast cancer

Karposi’s sarcoma

29
Q

How does taxol work?

A

Binds and stabilises microtubules

30
Q

What are the advantages of antisense therapy?

A
  • same effect as enzyme inhibitor or receptor antagonist
  • highly specific where oligonucleotide is 17 nucleotides or more
  • smaller dose levels required compared to inhibitors or antagonists
  • potentially less side effects
31
Q

What are the disadvantages of antisense therapy?

A
  • exposed sections of mRNA must be targeted
  • instability and polarity of oligonucleotides
  • short life time of oligonucleotides and poor absorption across cell membranes.

Pharm Y2S2 (26 decks)

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