Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Mechanism of Drug Action (Drugs) > Anti-cancer chemotherapy > Flashcards

Anti-cancer chemotherapy Flashcards

1
Q

What are the general classes of anti-cancer drugs?

A
  1. Cytotoxic drugs (inhibits process of cell division)
  2. Hormones
  3. Protein kinase (small molecule) inhibitors
  4. Monoclonal antibodies
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the classes of cytotoxic drugs?

A
  1. Alkylating/cross-linking agents
  2. Anti-metabolites
  3. Anti-mitotic drugs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the classes of alkylating/cross-linking drugs?

A
  1. Nitrogen mustards
  2. Nitrosureas
  3. Aziridines
  4. Platinum compounds
  5. Anthracyclines
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the mechanism of action of nitrogen mustards?

A

Alkylating agents form highly reactive carbonium ions (usually 2) that are able to:

  1. Cross-link nucleotide bases within the same strand of DNA or across different strands. This inhibits DNA replication/transcription.
  2. If first carbonium alkylates guanine and second carbonium ion reacts with water, the monoalkylated guanine may be misread (can pair with thymine) during DNA replication and there may be a GC → AT mutation.
  3. Alkylated strands are targeted by DNA repair mechanism and so may cause scission and fragmentation of DNA.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are examples of nitrogen mustards?

A
  1. Cyclophosphamide
  2. Chloambucil
  3. Melphalan
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the mechanism of activation of nitrosoureas?

A
  • Capable of alkylating DNA via carbonium ion
  • Guanine is preferred target
  • Creates interstrand cross-links that inhibit DNA transcription/replication
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are examples of nitrosoureas?

A
  • Carmustine

- Lomustine

  • Semustine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the mechanism of action of aziridines?

A
  1. First bond with DNA formed via reaction with semiquinone following breaking of the aziridine ring
  2. Second bond formed after displacement of carbamate from aziridine molecule
  3. Creates intra- and interstrand crosslinks in DNA
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are examples of aziridines?

A

Mitomycin C

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is the mechanism of action of platinum compounds?

A
  1. Plainer compounds with Cl atoms on the same side (Cis)
  2. Once it enters the cell, the molecule reacts with DNA via 2 mechanisms:
    - Via aquo intermediate
    - Direct binding
  3. It preferentially binds G and A
  4. Its primary action is to create intrastrand crosslinks between adjacent G molecules
  5. Causes bending of the DNA duplex and inhibits action of DNAP
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are examples of platinum compounds?

A

- Cisplatin

  • Carboplatin
  • Oxaliplatin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is the mechanism of action of anthracyclines?

A

Plainer structures that non-covalent interaction with DNA

  1. They insert into the spaces between the planes of different nucleotide base pairs in dsDNA following localised partial unwinding.
  2. Their intercalation into the dsDNA fixes the partially unwound nature of dsDNA, disrupting the sizes of the major/minor grooves in dsDNA.
  3. The different sized grooves disrupts the binding of DNA/RNA polymerases.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are examples of anthracyclines?

A
  • Doxorubicin
  • Daunomycin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the anti-metabolites?

A
  • Methotrexate
  • 5-fluorouracil
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the mechanism of action of methotrexate?

A
  • Inhibition of DHFR
  • Inhibits synthesis of purine nucleotides and thymidylate
  • Acts as competitive inhibitor of folate transport into mammalian cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is the mechanism of action of leucovorin?

A
  1. Leucovorin can be given in conjunction with methotrexate as it can be converted to folic acid derivatives
  2. Allows DNA synthesis to occur in normal cells but small amounts present don’t meet demands of fast dividing cancer cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is the mechanism of action of 5-fluorouracil?

A
  • Inhibitor of deoxythymidylate (DTMP) synthesis
  • Interacts with thymidylate synthetase but is not converted to DTMP
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What are the topoisomerase inhibitors?

A
  1. Etoposide
  2. Topotecan
19
Q

What is the mechanism of etoposide?

A
  • Inhibitor of topoisomerase II
  • Prevents DNA replication
20
Q

What is the mechanism of topotectan

A
  • Inhibitor of topoisomerase I
21
Q

What are the classes of anti-mitotic drugs?

A
  1. Topoisomerase inhibitors
  2. Vinca alkaloids
  3. Taxanes
22
Q

What is the mechanism of action of vinca alkaloids?

A
  1. Binds to free tubulin dimers in the cytosol
  2. Prevents them from polymerising into microtubule
  3. Shifts equilibrium of microtubule formation towards depolymerisation
  4. Disrupts formation of mitotic spindle and thus inhibits cell division
23
Q

What are examples of vinca alkaloids?

A
  • Vincristine
  • Vinblastine
24
Q

What is the mechanism of action of taxanes?

A
  1. Stabilises microtubules and shifts equilibrium towards polymerisation
  2. Causes formation of abnormal bundles of microtubules that disrupt mitosis and leads to cell death
25
Q

What are examples of taxanes?

A

- Paclitaxel

  • Docetaxel
  • Cabazitaxel
26
Q

What are the classes of hormone anti-cancer drugs?

A
  1. Anti-oestrogens
  2. Aromatase inhibitors
  3. GnRH analogues
  4. Anti-androgens
  5. Glucocorticoids
27
Q

What is the mechanism of action of anti-oestrogens?

A
  1. Competitive inhibitor of oestrogen receptors (ER)
  2. Reduces pro-proliferation effects of oestrogen
28
Q

What are examples of anti-oestrogens?

A

- Tamoxifen

- Toremifene

  • Fulvestrant
29
Q

What is the mechanism of action of aromatase inhibitors?

A
  1. Competitive inhibition of aromatase enzyme and inhibits synthesis of oestrogens in adrenal cortex, fats and muscles
  2. Effective in post-menstrual women whose ovaries no longer produce oestrogen
30
Q

What are examples of aromatase inhibitors?

A

- Anastrozole

  • Letrozole
31
Q

What is the mechanism of action of GnRH analogues?

A
  1. Normally, pulsatile release of GnRH stimulates release of LH from the anterior pituitary
  2. LH stimulates oestrogen release from ovaries and testosterone release from testes
  3. Continuous stimulation of anterior pituitary by GnRH causes desensitisation and inhibition of LH release
32
Q

What are examples of GnRH analogues?

A

- Goserelin

  • Buserelin
  • Leuprorelin
33
Q

What is the mechanism of action of anti-androgens?

A
  1. Competitive inhibitor of androgen receptor (AR)
  2. Inhibits activity of testosterone and other androgens
34
Q

What are examples of anti-androgens?

A

- Flutamide

  • Cyproterone
35
Q

What is the mechanism of action of prednisone (glucocorticoid)?

A
  1. Prodrug that is converted to active prednisolone in liver
  2. Upregulates expression of anti-inflammatory proteins and suppresses lymphocyte proliferation
36
Q

What are the monoclonal antibody anti-cancer drugs?

A
  1. Rituximab
  2. Trastuzumab
  3. Bevacizumab
  4. Cetuximab
37
Q

What is the mechanism of action of rituximab?

A

Humanised monoclonal antibody

  1. Binds to CD20 on surface of transformed B cells
  2. Mediates lysis of these B cells through variety of antibody-specific mechanisms
38
Q

What is the mechanism of action of trastuzumab?

A

Humanised monoclonal antibody

  1. Binds to humanised epithelial growth factor 2 (HER2/hEGFR2)
  2. Inhibits binding of EGF and promotes cell proliferation
39
Q

What is the mechanism of action of bevacizumab?

A

Humanised monoclonal antibody

  1. Binds to and inhibits action of VEGF
  2. Prevents angiogenesis and thus inhibits tumour growth
40
Q

What is the mechanism of action of cetuximab?

A

Human/mouse chimeric monoclonal antibody

Binds to EGFR and inhibits binding of EGF

41
Q

What are example of a protein kinase (small molecule) inhibitor?

A
  1. Imatinib
  2. Erlotinib
42
Q

What is the mechanism of action of imatinib?

A

Inhibitor of EGFR protein kinases:

  1. Bcr-Abl chimeric protein (chronic myeloid leukemia)
  2. C-kit

Inhibition is achieved by binding to ATP-binding site

43
Q

What is the mechanism of action of erlotinib?

A
  1. Inhibits EGFR tyrosine kinase
  2. Prevents down-stream signalling and EGF pro-proliferation signals

Mechanism of Drug Action (Drugs) (26 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions