Brainscape's Knowledge GenomeTM

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


See full index

Y1 - Pharm > 12_Cell Cycle II > Flashcards

12_Cell Cycle II Flashcards

1
Q

list some of the purine antagonists?

A
  • hypoxanthine
  • 6-mercaptopurine
  • allopurinol
  • guanine
  • 5-thioguanine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

which drugs at at PRPP in the pathway?

(Phosphoribosyl pyrophosphate (PRPP)

A
  • 6-TG: thioguanine
  • 6-MP: mercaptopurine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

where in the cycle are the purine antagonists act in the biosynthetic pathways?

A
  • acts on rNMP, preventing the conversion into rNDP –> preventing formation of RNA and DNA –> apoptosis
  • mercaptopurine and thioguanine: both stops the use of purines;
    • prevents the salvage pathway from creating purines
    • can’t enter replicatoin–> apoptosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

in which cell cycle phase does the purine antagonists act?

A

acts on the S phase;

prevents replication/formation of DNA/RNA

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

mercaptopurine:

admin, indications, mechanism

A
  • admin: oral
  • indications:
    • acute lymphocytic leukemia
    • acute lymphatic leukemia
  • mech:
    • corresponding nucleotide –> inhibits enzymes involved in purine nucleotide interconversion
    • misincorporation into DNA and RNA
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

mercaptopurine:

toxicity

A
  • acute: no acute toxicity
  • delayed:
    • myelosuppression
    • immunosuppression
    • hepatoxicity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

thioguanine:

admin, indications, mech

A
  • admin: ORAL
  • indications:
    • acute adult leukemia
    • synergy w/ cytarabine
  • mech:
    • inhibition of purine nucleotide interconversion
    • misincorporation into DNA and RNA
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

thioguanine:

toxicity

A
  • acute:
    • no acute toxicity
  • delayed
    • myelosuppression
    • immunosuppression
    • hepatotoxicity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

allopurinol:

use

A
  • used to decrease high blood uric acid levels; CO-ADMINISTERED when pt is given purine antagonist drugs
  • administered as supportive therapy w/ chemotherapeutic agents:
    • prevent gout,
    • prevent specific types of kidney stones and
    • for the high uric acid levels that can occur with chemotherapy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

which drug degrades purine antagonist to act as a cancer chemo drug?

A

xanthine oxidase;

which acts on allopurinol and hypoxanthine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

how is uric acid formed?

A

HYPOXANTHINE –[xanthine oxidase]–> XANTHINE –[xantine oxidase]–> URIC ACID

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

by what mechanism does allopurinol help with supportive therapy?

what caution must be noted?

A
  • in chemo, purine analogues are degraded by xanthine oxidase
  • ALLOPURINOL administered –> inhibits xanthine oxidase –> to maintain drug concentration

CAUTION: when allopurinol is used, need to LOWER PURINE ANTAGONIST DOSE to PREVENT TOXICITY

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

list the antimitotic drugs?

are these structural analogs of anything in the cell?

A
  • EXAMPLES
    • vincristine
    • vinblastine
    • paclitaxel
    • docetaxel
  • these are NOT structural analogs of anything in the cell; these are different agents
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

where in the cell cycle do anti-mitotics act?

how does it function?

A
  • **acts during M PHASE
  • inhibit polymerization of microtubules by activating the spindle assembly checkpoint (SAC) –> blocking transition from metaphase to anaphase
  • cells undergo mitotic arrest
    • since the compound disrupts spindle formation and chromosome orientation, –>
    • cells remain either in a prolonged arrest state with subsequent apoptosis induction or in a senescence-like G1 state
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

during which cell cycle PHASE do the anti-mitotics act?

A

docetaxel and pacitaxel act during M phase

(mitotic phase)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

what is the detailed mechanism of action of anti-mitotic drugs: vincristine/vinblastine?

A
  • these drugs are alkaloid derivatives of plants –> acting as spindle poisons
    • Depolymerize MTs –> disrupting cytoskeletal structure
      *
17
Q

which anti-mitotics enhance tubulin polymerization?

A
  • paclitaxel and docetaxel both enhance tubulin polymerization; preventing chromosomes from separating
    • “suppression of microtubule dynamics”
  • bind specifically to dimeric form of tubulin –> cannot achieve spindle configuration for mitosis –> mitotic arrest at metaphase –> apoptosis
18
Q

VINBLASTINE:

indications, adverse effects

A
  • indicated for: systemic Hodgkin’s disease
  • adverse effects:
    • acute: nausea and vomiting
    • delayed: marrow suppression and alopecia
19
Q

VINCRISTINE:

indications, adverse effects

A
  • indication: combination chemo w/ prednisone in acute leukemia in children (pt of CHOP protocol)
  • adverse effects:
    • **ONLY DELAYED TOXICITY: significant incidence of neurotoxicity
20
Q

PACLITAXEL:

indications, adverse effects

A
  • indicated for: ovarian CA, advanced breast CA
  • adverse effects:
    • acute: nausea/ vomiting. hypotension, arrythmias
    • delayed: bone marrow suppression,
21
Q

DOCETAXEL:

indications, adverse effects

A
  • indicated for: breast, prostate, and non-small cell cancers
  • adverse effects:
    • *DELAYED ONLY: alopecia and hematological effects
22
Q

which two antimitotics display ONLY DELAYED ADVERSE EFFECTS?

A
  • VINCRISTINE and DOCETAXEL;
  • Doc Cristine - delayed
23
Q

process of a bacterial mutation analysis

A
  • (administering tumor-causing drugs into patient – using SELECTIVE PRESSURE to determining effects)
    1. tx cells w/ an agent that induces mutations
    2. grow cells on media which SELECTS FOR these mutations
    3. only cells w/ that mutation will grow
    4. subsequently will form colonies (only those that are mutated/resistant would be able to do so)
24
Q

how is bacterial mutation analysis relevant to cancer therapy?

A
  • many agents induce mutations (esp cell cycle non-specific drugs);
    • alkylating agents, antibiotics
  • as pt receives therapy –> cancer cells are exposed to mutagens
  • mutant cells selected by their ability to grow while tx continues
25
Q

why is it important to knock out ALL mutated cells whil administering chemo?

A

if not, that ONE resistant cell will amplify over the subsequent treatment cycles

  • so if you knock out all but one –> then it will continue to proliferate;
  • YOU NEED TO HAVE A MECHANISM to knock out the resistant cell (using combination chemo)**
26
Q

when genes amplify, what occurs?

A
  • increase in GENE COPY NUMBER
  • increase in GENE PRODUCT

Clinical dose is RENDERED INEFFECTIVE (bc there’s so much of the gene, and can’t inc the dose enough)

27
Q

what alterations in protein structure occurs when a cell becomes resistant to cancer chemo?

A
  • classical mechanism: change in gene structure w/o amplification
  • gene product displays different protein characteristics
    • mutation analysis; if pt has cancer –> this can be lethal for the patient
28
Q

how does a cancer cell become resistant with decreased enzyme activity (mechanisms)?

A
  • decreased gene expression of proteins required for drug metabolism
  • active analogues not synthesized (administered as prodrugs)
29
Q

mechanism of P-glycoprotein alteration (aka multi-drug resistance protein) becoming resistant to cancer chemo

(and examples)

A
  • P-glycoprotein involved in membrane transport
  • change in p-glycoprotein alters drug transport into cell or increases its removal from tumor cell

examples:

  • methotrexate: decreased uptake
  • vinca alklaloids: decreased uptake
30
Q

what is the purpose of combination chemotherapy, and

how does it work?

A
  • if multiple drugs administered together; will be sure to kill all cells (even if they’re resistant to a certain drug)
31
Q

DNA repair: functions

A
  • In normal cells, DNA repair functions to maintain the integrity of cellular genetic
    information (allows it to go back)
  • In tumor cells, identical pathways reduce drug efficacy by removal of DNA lesions
    formed during therapy
  • Applies to both chemotherapy and radiation therapy
32
Q

DNA repair and cancer chemotherapy?

A
  • DNA can be an impediment to effective therapy
  • laboratories studied the effects of radiation –> discovered DNA repair pathways
33
Q

which damaging agents can be corrected by DNA repair pathways?

A
  • strand breaks
  • intercalation
  • free radical formation
  • alkylation
34
Q

which drug is used for gliomas?

mechanism?

A
  • Temozolomide (Temodar)
    • Alkylating agent used to tx glioma (brain cells have DNA repair pathways too)
    • mech: inducses DNA lesions
  • DNA repair:
    • temodar induced lesions removed by the DNA repair enzyne, O6-alkylguanine alkyltransferase

Y1 - Pharm (12 decks)

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