Brainscape's Knowledge GenomeTM

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


See full index

23 spring: pharm > Test 3: 43 and 44: anticancer drugs > Flashcards

Test 3: 43 and 44: anticancer drugs Flashcards

1
Q

3 hallmarks of cancer

A

unrestricted cell division
tissue invasion and metastasis
sustained angiogensis

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

S phase of cell cycle

A

DNA synthesis/replication

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

log kill hypothesis for cancer treatment

A

One round of chemotherapy:
kills a constant fraction of cells;
does not kill all tumor cells

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

what are some mechanisms for drug resistance in cancer cells

A
  • Gene amplification
  • Qualitative changes in drug target
  • Enhanced DNA repair pathways
  • Multi-drug resistance protein
  • Increased pools of reduced glutathione (inactivate alkylating drugs)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

P-glycoproteins on cancer cell membrane do what

A

push drug out of cancer cell

leads to multi drug resistance

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

goal of metronomic chemotherapy

A

desired endpoint for metronomic chemotherapy is stabilization of disease rather than an overall reduction or elimination of tumor

low dose cytotoxic drug given at regular intervals= less toxic and less expensive

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Requirements for effective combination cancer therapy

A
  • Drugs must be individually active
  • Each drug must act via different mechanism
  • Drugs should have different toxicities
  • Intense intermittent schedules
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

what are some alkylating cancer drugs

A

derived from mustard gas

  • Bis(chloroethyl)amines (Cyclophosphamide, chlorambucil)
  • Ethylenimines
  • Alkylsulfonates
  • Nitrosoureas (Carmustine, semustine, lomustine)
  • Platinum drugs (not true alkylators)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

how do alkylating cancer drugs work

A

Add alkyl group radicals to DNA
– intra and inter strand Crosslink DNA at guanine (damage DNA)

leads to single and double stranded breaks → misreading of genetic code

interferes with DNA replication (S phase and transcription)

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

effects of DNA alkylation with cancer meds

A
  • Intra and inter-strand crosslinking
  • Single and double stranded breaks
  • Misreading of genetic code
  • Guanine depurination

Interferes with DNA replication -S phase & transcription -cell cycle non-specific (CCNS)

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

adverse effect of alkylating drugs

A

! Cytotoxic
! Immunosuppressive
! Infertility
! Nausea, vomiting (GI)
! Mutagenic
! Teratogenic
! Carcinogenic

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

how do cancer cells become resistant to alkylating drugs

A

increase glutathione- will bind to alkylating agents and prevent them from binding to DNA

increase DNA repair- remove cross links

decreased cellular permeability

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

Bis(chloroethyl)amines: Cyclophosphamide

A

alkylating anticancer drug derived from mustard gas

metabolized in liver to acrolein which is excreted in urine but can be bladder irritant

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

what is acrolein

A

byproduct of the breakdown of alkylating anticancer drug: Bis(chloroethyl)amines: Cyclophosphamide

acrolein irritates the bladder mucosa and can lead to hemorrhagic cystitis

negative effects can be reduced
w/ diuresis and increased water intake

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

chlorambucil

A

alkylating anticancer: Bis(chloroethyl)amine

slower acting than cyclophosphamide but does NOT cause hemorrhagic cystitis

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

can Bis(chloroethyl)amine anticancer drugs cross the BBB

A

no

17
Q

can nitrosoureas anticancer drug cross the BBB

A

yes

carmustine, lomustine, semustine

18
Q

how do nitrosoureas anticancer drugs work

A

prodrug: metabolized into Carbonium ions and Isocyanate

Carbonium ions- can alkyate nucleophiles and cause crosslinking of DNA

Isocyanate: Carbamylates proteins (inhibits protein function)

carmustine, lomustine, semustine
can cross BBB

19
Q

how do platinum anticancer drugs work

A

act similar to alkylating agents

form crosslink DNA at guanine and cytosine

Interferes with DNA replication (S phase)

cisplatin, carboplatin

20
Q

can cisplatin cross the BBB

A

no

platinum anticancer drug: acts like alkylating drugs: cause crosslink in DNA that interferes with DNA replication (S phase)

21
Q

what will happen to cat if you give cisplatin

A

severe pulmonary toxicity

cisplatin: platinum anticancer drug: acts like alkylating drugs: cause crosslink in DNA that interferes with DNA replication (S phase), poor BBB penetration, builds up in kidney and liver

22
Q

what are two types of anti metabolites anticancer drugs

A

folic acid antagonists
pyrimidine antagonists

23
Q

how does methotrexate work

A

anticancer drug
folic acid analog

Competitively inhibits dihydrofolate reductase (DHFR)
– Inhibits DNA synthesis (indirect)
– Also interferes with RNA and protein synthesis

24
Q

— converts folate to FH 2 (dihydrofolate)
and FH4 (tetrahydrofolate)

A

dihydrofolate reductase (DHFR)

FH4 is then used to make:
* thymidylate (dTMP)
* purine nucleotides
* methionine and serine amino acids

methotrexate- anticancer drug that competitively inhibits DHFR

25
Q

can methotrexate get into brain

A

yes

methotrexate- anticancer drug that competitively inhibits DHFR

26
Q

how to reverse toxicity of methotrexate

A

leucovorin (synthetic FH4)

methotrexate- anticancer drug that competitively inhibits DHFR

27
Q

mechanism of methotrexate resistance

A
  • Mutations in DHFR that lower affinity for MTX
  • DHFR gene amplification
  • Decreased drug transport

methotrexate- anticancer drug that competitively inhibits DHFR

28
Q

— is a pyrimidine antagonist anticancer drug

A

Cytarabine (cytosine arabinoside; AraC)

prodrug- once activated cytotoxic to proliferating cell

Prevents DNA synthesis and inhibits DNA repair

29
Q

how do vinca alkaloids work

A

derived from plant

binds to tubulin and disrupts microtubule structure (M phase)

promote microtubule disassembly

Vincristine, Vinblastine, Vinorelbine, Vinflunine

30
Q

how do cancer cells develop resistance to vinca alkaloids

A

increase MDR1 (P-glycoprotein)

channel that pushes drug out of cancer cell

31
Q

doxorubicin

A

anticancer antibiotics

Intercalating agent- Primarily blocks DNA synthesis (S phase)

slips inbetween DNA and forms complex that can not be unwound→ Inhibits topoisomerase II (Fragments DNA

32
Q

3 activities of doxorubicin

A

DNA intercalation → leads to DNA breakage

generates Oxygen free radicals → helps break DNA, damaged cardiac cell membranes

alters fluidity of cell membrane

antibiotic anticancer med

33
Q

adverse effects of doxorubicin

A

cumulative cardiac toxicity
tissue necrosis
hemorrhagic enteritis

antibiotic anticancer med- forms DNA intercalation which results in DNA breakage

34
Q

actinomycin D will cause —

A

single stranded breaks in DNA

inhibits DNA and RNA synthesis

intercalates DNA between guanine-cytosine base pairs

antibiotic anticancer med

35
Q

Bleomycin does not cause — like actinomycin D

A

myelosuppression

antibiotic anticancer med: binds to guanine base and forms bleomycin-Fe(II) DNA → free radical formation and DNA breakage

36
Q

bleomycin cause cancer cells to accumulate in —

A

G2 phase

antibiotic anticancer med

37
Q

how does bleomycin work

A

binds to guanine bases and form complex that cause release of free radicals

leads to DNA breaks

antibiotic anticancer med- no myelosuppression and cause cells to get stuck in G2 phase

38
Q

adverse effects of bleomycin

A

lung toxicity and fibrosis

No significant myelosuppression (bone marrow sparing)(unlike actinomycin D)

antibiotic anticancer meds

23 spring: pharm (46 decks)

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