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Flashcards in Anticancer Deck (65)
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1

cancer drugs overview 

2

describe primary, adjuvent, and neoadjuvent chemotherapy

  • Primary: when neoplasms are disseminated and not amenable to surgery
  • Adjuvent: used to attack micrometastases following surgery and radiation
  • Neoadjuvent: Given prior to surgery to shrink the cancer

3

which cells are most sensitive to anticancer drugs?

  • rapidly dividing cells
    • buccal mucosa (stomatitis)
    • bone marrow (myelosuppression)
    • GI mucosa (nausea vomit)
    • hair cells (alopecia)

4

describe cell-cycle specific drugs

  • Exert action on cells traversing cell cycle, most effecting in hematologic malignancies, useful in high growth-fraction tumours 
  • Antimetaboites (S-phase)
  • Bleomycin (G2-phase) 
  • Camptothecins 
  • Epipodophyllotoxins (late S-G2 phase)
  • Microtubule inhibitors (metaphase arrest)

5

describe cell-cycle nonspecific drugs

  • kill tumour cells whether they are cycling (more sensitive) or in Go resting phase, useful in low and high growth-fraction solid tumours 
  • Alkylating agents (can cause treatment induced neoplasms)
  • Platinum coordination complexes
  • Antitumour antibiotics

6

list high, medium, and low myelosuppression drugs

  • High
    • Cytarabine
    • Alkylating Agents
    • Doxorubucin and Daunorubucin (antitumour anitbiotic)
    • Vinblastine (vinca alkaloid)
  • Medium
    • Carboplatin
    • Methotrexate (antimetabolite)
    • 5-fluorouracil (antimetabolite)
  • Low
    • Bleomycin (antitumour anitbiotic)
    • Vincristine (vinca alkaloid)
    • Asparaginase

7

doxorubicin toxicity

cardiotoxicity - anticancer antibiotic

8

cyclophosphamide toxicity

hemorrhagic cystitis

9

bleomycin toxicity

pulmonary fibrosis

10

vincristine and paclitaxel toxicity

peripheral neuropathy

11

rescues bone marrow from methotrexate (methotrexate antidote)

Leucovorin

12

reduces hemorrhagic cystitis from cyclophosphamide

Mesna

13

reduces anthracycline-induced cardiotoxicity (ex. from doxorubicin)

Dexrazoxane

14

reduces renal toxicity caused by cisplatin

Amifostine

15

list antimetabolites and the phase it acts on 

  • S-phase
  • folate analog: Methotrexate
  • purine analogs: 6-mercaptopurine (6-MP), 6-thioguanine (6-TG)
  • pyrimidine analogs: 5-fluorouracil (5-FU), Capecitabine, Cytarabine

16

Methotrexate MOA

 

 

Inhibits DHF reductase → deprives cells of folate → dTMP and purine nucleotide synthesis decreases → RNA/DNA/protein synthesis decreases → cell death 

Undergoes conversation to a series of polyglutamates (MTX-PGs)

17

methotrexate AEs

  • Renal damage (from high-dose)
  • Hepatic fibrosis 
  • Cirrhosis, pneumonitis, neurologic toxicities (IT administration)
  • Common: stomatitis, mucositis, myelosuppression, alopecia, nausea, vomiting

18

Leucovorin MOA

  • N5-formyl-THF
  • antidote for drugs that decrease folic acid (like methotrexate)
  • rescues bone marrow
  • provides normal tissues with reduced folate, circumventing the inhibition of DFHR

19

Clinical use of Leucovorin

  1. Rescues bone marrow suppression from MTX
  2. Potentiates effect of 5-FU

20

effects of Allopurinol

Potentiates 6-MP

No effect on 6-TG

21

6-Thioguanine treats which cancer specifically? 

Acute nonlymphocytic leukemia

22

6-Mercaptopurine MOA

Converted to thio-IMP by HGPRT (purine salvage pathway) → inhibits 1st step of de novo purine synthesis 
Thio-IMP also blocks formation of AMP and GMP
Dysfunctional RNA and DNA result from incorporation of guanylate analogs

23

xanthine oxidase

Metabolizes 6-MP to thioruic acid

24

If ___ is given to reduce ___, dose of 6-MP must be DECREASED to avoid accumulation

If allopurinol is given to reduce hyperuricemia, dose of 6-MP must be DECREASED to avoid accumulation

25

6-MP and 6-TG AEs

  • Nausea, vomiting, diarrhea
  • bone marrow suppression,
  • hepatotoxicity (6-MP)

26

6-thioguanine (6-TG) MOA

converted to nucleotide →  inhibits purine synthesis and phosphorylation of GMP to GDP, can be incorporated into RNA and DNA

27

5-FU inhibits ___ resulting in ____.

5-FU inhibits thymidylate synthase resulting in 'thymineless death'.

28

Combination chemotherapy used for colorectal cancer

5-FU and LEUCOVORIN


Leucovorin increases N5,N10-methylene-THF, potentiating 5-FU (which inhibits thymidylate synthase)

29

5-FU and Capecitabine AEs

  • HAND-FOOT SYNDROME: erythematous desquamation of the palms and soles seen after extended infusions

30

Cytarabine (ARA-C) MOA

(deoxycytidine analog) 

phosphorylated to triphosphate → incorporated into DNA → inhibits DNA polymerase

"tara takes double penetration"