Brainscape's Knowledge GenomeTM

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


See full index

MODA Lent > Chemotherapy > Flashcards

Chemotherapy Flashcards

1
Q

Three main classes of man-made synthetic antibiotics?

A

1) Sulfa drugs (sulfamethoxazole)
2) Fluoroquinolones (ciprofloxacin)
3) Oxazolidinone (linezolid)

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

Bacteriostatic

A

Antibiotics that stop bacteria or fungi from growing, exemplified by chloramphenicol

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

Bactericidal

A

Antibiotics that cause cell death. lower the cell count of the infection organism - for example penicillin

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

MIC

A

Minimal inhibitory concentration - lowest concentration of a drug that prevents growth of a particular bacterium

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

MBC

A

Minimal bacterial concentration - lowest concentration that kills the bacterium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Nitrogen Mustards (Melphalan/Cyclophosphamide)

A

Drugs that bind covalently with DNA to prevent effective DNA replication and gene expression

  • Very reactive, cell-cycle-phase non specific compounds that cause ALKYLATION OF DNA (covalently link alkyl groups to chemical moieties in nucleic acids + proteins)
  • Cross links formed between or within DNA strands
  • DNA repair mechanisms recognise alkylated DNA and will attempt to repair
  • Reactions can occur with other nucleophilic groups in DNA/RNA –> cause for general toxicity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Antimetabolites

A

Drugs that inhibit DNA/RNA biosynthesis in 2 ways…

1) Inhibition of normal precursor production
2) Substitution of purines/pyramidines in nucleic acid synthesis

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

Cyclophosphamide

A
  • Nitrogen Mustard used against lymphoid tumour/ carcinomas
  • Needs to be metabolised in the liver by cytochrome P450 system to become activated to PHOSPHORAMIDE MUSTARD
  • Administered orally
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Melphalan (L-phenylalanine Mustard)

A

As phenylalanine is a precursor of melanin, melphalan accumulates in melanomas (pigmented skin tumours)

  • Administered orally
  • UNLIKE other Nitrogen Mustards, it will accumulate in tissue
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Nitrosoureas

A

Alkylating + Carbamoylating agents

  • React with a variety of groups to attach an alkyl (RCH2) or carbamoyl (RNCO) moieties
  • All nitrosoureas can produce interstrand cross links in duplex DNA in which N7 and O6 positions in guanine are preferred sites of attack
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Carmustine + Lomustine (Nitrosoureas)

A
  • Contain at least one chloroethyl side chain
  • Reduction in white blood cells/platelets and damage to various organs limits their usefulness
  • More lipophilic than nitrogen mustards - excellent brain penetration - important in the treatment of brain tumours
  • Carmustine given intravenously; Lomustine orally bioactive (60%)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Mitomycin C (Aziridine)

A
  • Contains 3-membered aziridine rings –> active anti-tumour drug
  • Antibiotic that selectively inhibits DNA synthesis in both bacteria and tumour cells. Inhibition via DNA alkylation and cross linking
  • Activation by chemical/enzymatic reduction of the quinone moiety.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Cisplatin (Cis-diamine dichloroplatinum)

A
  • Only active in its Cis form/ Transplatin is inactive
  • Is a cross linking agent in DNA, principal sites of action are the N7 atoms of guanine and adenine
  • Induces intrastrand cross links (GG 65%/ AG 22%) which causes major bending of dsDNA, with changes in major groove
  • Interstrand cross-links - 10%
  • Improved treatment of testicular cancer
  • Not used orally (only IV)
  • Inactivated by reaction with SH groups in glutathione _ metallothioneins
  • Harmful effects = Renal toxicity + bone marrow suppression
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

How do Carboplatin and Oxaliplatin compare to Cisplatin?

A

More favourable toxicity profiles i.e. less renal toxicity or bone marrow suppression

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What happens when DNA damage caused by alkylation and cross linking is beyond repair?

A

Results in the synthesis of p53, a tumour suppressor/transcription factor that drives the expression of genes for:

  • growth arrest
  • DNA repair
  • apoptosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

2 types of drugs that bind non-covalently with DNA to prevent effective DNA replication and gene expression?

A
  • Anthracyclines (doxorubicin/daunorubicin)

- Actinomycins (actinomycin D)

17
Q

What is the general mechanism employed by anti-cancer agents that bind non-covalently to DNA

A

Have a planar aromatic ring structure that allows them to intercalate between stacked nucleobases at the centre of duplex DNA.
- Intercalation causes local unwinding on helix - changes in the geometry of minor/major groove –> affect binding of DNA and RNA polymerases + transcription factors

18
Q

Anthracyclines/ Daunomycin (Non-covalent)

A

Alongside intercalation which causes local unwinding - they cause generation of free radicals due to the presence of hydroxyquinone moiety –> free radicals attack DNA, inducing DNA cleavage
- Can also cause lipid peroxidation in cardiac tissue (cardiotoxicity)

19
Q

Mitoxantrone

A

Anthracycline analogue with a modified structure - does not generate free radicals
- Used in treatment of breast cancer/acute myeloid leukaemia/certain lymphomas

20
Q

Give examples of the 2 types of topoisomerase inhibitors…

A

Topoisomerase inhibitors will affect DNA replication as these enzymes are required to untangle and relax specific regions of DNA to allow transcription and replication

Type I - Camptothecins/ Topotecan
Type II - Etoposides/ Anthracyclines/ Mitoxantrone/ Epipodophyllotoxins

21
Q

Antimitotic drug/ Vinca Alkaloids

A

Drugs that bind to free tubulin dimers and lead to the disassembly and disappearance of microtubules - inhibit DNA replication
- Mitotic spindle poison that acts on microtubule formation

22
Q

Taxol (paclitaxel)

A
  • Disrupts equilibrium between free tubular dimers and microtubules by shifting it in the direction of assembly rather than disassembly
  • Bind to microtubules + stabilise these structures –> stabilisation of ordinary cytoplasmic microtubules and formation of abnormal bundles of microtubules
23
Q

Methotrexate

A
  • Folic acid antagonist
  • Inhibits enzyme DHFR (Dihydrofolate Reductase) which prevents conversion of Folic Acid to Dihydrofolate, and the conversion of Dihydrofolate to Tetrahydrofolate.
  • Competes with folic acid for active transport into normal cells
  • Intense use is associated with toxicity to normal tissue
24
Q

Leucovorin

A

Salvage normal tissues from folate depletion –> has vitamin activity equivalent to folic acid.

  • Does not require DHFR; so its function as a vitamin is unaffected by methotrexate
  • Allows pyrimidine synthesis to occurs in the presence of DHFR inhibition
  • Can reduce methotrexate inhibition in normal cells alone due to differences in the tetrahydrofolate requirement…
25
Q

Action of folate antagonists?

A

Usually inhibit enzyme action (DHFR) to INDIRECTLY affect thymidine production

26
Q

5-fluorouracil (5-fluoro-2-deoxyuridine)

A
  • Pyrimidine antagonist/ dUMP analogues
  • Inhibition of thymidylate synthetase is the primary cytotoxic mechanism
  • Can also be incorporated into rRNA and mRNA inhibiting transcription/ intracellular distribution/ translation
27
Q

6-mercaptopurine/ 6-thioguanine

A
  • Purine antagonists
  • Analogues of hypoxanthine and guanine, respectively
  • Thiopurines will inhibit nucleotide synthesis, as well as being incorporated into nucleic acids
28
Q

How do steroid hormones (testosterone/estradiol) contribute to the proliferation of certain types of tumours?

A 
Steroid hormones (lipophilic) bind to nuclear receptors; interact hormone response elements in DNA to regulate the expression of genes responsible for the physiological effects of the hormones
e.g. breast cancers will grow more rapidly in the presence of oestrogen...
29
Q

Tamoxifen

A

Anti-oestrogen that competitively binds to oestrogen receptors (in breast tissue) but with lower affinity than oestrogen.

  • Tamoxifen-oestrogen receptor complex translocates to the nucleus –> transcription of oestrogen-responsive genes involved in the development of breast cancers is attenuated
  • Tamoxifen can exert oestrogen agonist effects in bone and uterus (endometrial proliferation)
30
Q

Toremifene

A

Tamoxifen analogue without oestrogen agonist properties

- Improved agent

31
Q

Anastrazole

A

Inhibits aromatase enzyme, which mediates the final step in the oestrogen synthesis pathway in fat and muscle in post-menopausal women (androgen precursors –> estradiol)
Why? Elevated levels of circulating oestrogen linked to breast cancer

32
Q

Trastuzumab (Herceptin)

A

Binds to extracellular domain of human epidermal growth factor 2 (HER2) and prevents binding of EGF.
- HER2 over expressed in 25-30% of breast cancers
- IV administration
Side effects: chills, asthenia (abnormal physical weakness), fever, nausea and in some rare cases cardiac dysfunction

33
Q

Goseraline

A
  • Drug against prostate cancer (biochemical castration)
  • GnRH synthetic homologue, that acts as a strong agonist on the GnRH receptor. Sustained agonist binding at the GnRH receptor results in complete inhibition of testosterone synthesis
34
Q

Bevacizumab

A

Humanised monoclonal antibody that binds to and inhibits human vascular endothelial growth factor (VEGF) - soluble protein important in blood vessel formation. Anti-angiogenic limit the the growth of tumours
- Used in metastatic colorectal cancer (with 5-fluoro-uracil) lung cancer + breast cancer
Side effects: interfere with wound healing/ increase risk of bleeding/ gastrointestinal perforation/ hypertension/ proteinuria

35
Q

Rituximab

A

Humanised monoclonal antibody against CD20 - protein present on the surface of transformed B cells in Hodgkin’s disease and non-Hodgkin lymphoma

  • Lyse CD20 cells via antibody-dependent cell mediated cytotoxicity
  • Activation of complement cascade
  • Introduction of apoptosis
36
Q

Erlotinib

A

Inhibits EGFR tyrosine kinases

  • Orally active/ potent
  • Toxicity: skin rashes and diarrhoea
37
Q

Toceranib + Mastinib

A

Tyrosine kinase inhibitors - used in the treatment of non-resectable grade II-III mast cell tumours in the connective tissue of dogs

38
Q

Imatinib

A

Small molecule inhibitor

  • Inhibits Bcr-Abl tyrosine kinase (fusion gene due to the Philadelphia chromosome) –> main cause of CML
  • Also inhibit c-kit, tyrosine kinase growth factor receptor in mast cells, over-expressed in gastrointestinal stromal tumours (GISTs)
39
Q

How are anticancer drugs selective?

A

1) Differential accumulation - Tumour cells have a higher rate of glycolysis - lower intracellular pH - drugs become trapped in tumour cells through protonation
2) Differential activation - Drugs activated by reduction have enhanced toxicity in hypoxic tumour cells
3) Differential importance - greater level of DNA replication + cell division in tumour cells.

MODA Lent (3 decks)

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