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Emma Heme/Onc > Pharm - Antitumor Abx/Plant Alkaloids > Flashcards

Pharm - Antitumor Abx/Plant Alkaloids Flashcards

1
Q

Ant-tumor abx

A

anthracyclines (doxorubicin)

bleomycin, dactinomycin, mitomycin

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2
Q

plant alkaloids

A

Topoisomerase I inhibitors
Vinca alkaloids
Taxanes

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3
Q

Topoisomerase I inhibitors

A

irinotecan

topotecan

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4
Q

vinca alkaloids

A

vinCRistine

vinBLastine

vinorelbine

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5
Q

taxanes

A

paclitaxel

docetaxel

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6
Q

anthracyclines

MOA

A

passive diffusion of unionized drug into cells

all nucleated cells can rapidly accumulate drug

intercalate DNA - accumulates in nucleus

topoisomerase II inhibitor

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7
Q

anthracyclines clearance

A

mostly liver

monitor bilirubin

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8
Q

anthracyclines

major dose-limiting side effect

A

myelosuppression (neutropenia)

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9
Q

anthracyclines

A 
myelosuppression
alopecia
N/V
Urine
Vesicant
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10
Q

cardiotoxicity w/ anthracycline use

A

undergo 1 or 2 electron reductions to reactive compounds

oxygen radical formation

(semiquinone +O2=O2 free radical)

uses Fe3+ to form reactive species (OH-)

acute: EKG changes, arrhythmias
chronic: cumulative doses LVEF, dilation, congestion, effusions

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11
Q

____ is more susceptible to the oxidative damage caused by anthracyclines

A

myocardium

has dec endogenous antioxidant enzymes (glutathione)

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12
Q

preventative cardioprotection during anthracycline use

A
  • weekly admin (versus q3week) to avoid high peaks
  • chelating agent
  • liposomal products
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13
Q

dexrazoxane

A

hydrolyzed to EDTA-derived analog

chelator, binds intracellular Fe to dec free radical formed w/ anthracycline use

FDA approved - metastatic breast cancer

GIVEN W/I 30 MIN OF DOXORUBICIN

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14
Q

dexrazoxane AE

A 
myelosuppression
alopecia
mucositis
N/V
diarrhea

*unsure if via dexrazoxane alone or combo w/ anthracycline

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15
Q

liposomal anthracyclines

A

Doxil

avoids high peak concentrations of anthracyclines

(avoids free radical damage, cardiotoxicity)

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16
Q

anthracycline resistance

A
  • active efflux from cells (MDRp170)
  • altered topoisomerase II
  • altered free radical biochem (inc glutathione - antioxidant)
17
Q

daunorubicin/idarubicin use

A

leukemias

18
Q

doxorubicin/epirubicin use

A

breast

lymphomas

19
Q

dactinomycin use

A

Wilm’s
Ewing’s
germ cell

20
Q

bleomycin use

A

hodkins
sclerosis for pleural effusions
lung tox

21
Q

mitomycin-C use

A

bladder cancer
anal cancer
long nadir (4-6 wks)

22
Q

camptothecins

A

irinotecan

topotecan

23
Q

topotecan use

A

ovarian

24
Q

irinotecan use

A

GI

25
Q

topotecan AE

A
  • neutropenia
  • thrombocytopenia
  • GI (mild): mucositis, N/V/D
  • alopecia
  • rash
  • elevated LFTs
26
Q

irinotecan

AE

A
  • neutropenia
  • thrombocytopenia
  • eosinophilia
  • GI * DIARRHEA (cholinergic)

-N/V, alopecia, asthenia, anorexia, fatigue, inc LFTs, bilirubin, term rxn

27
Q

irinotecan

2 types of main GI side effect

A
  • early onset=cholinergic syndrome, tx w/ atropine

- late onset=SN-38 metabolite, changes in gut epithelium

28
Q

topo I inhibitor resistance

A
  • reduced drug accumulation
  • altered intracellular drug distribution
  • altered carboxyl esterase activity
  • dec levels of topo I (dec transcription, mutations)
  • low S-phase fraction of cancer cells
29
Q

topo I

A

S-phase
-relaxes supercoiled DNA by creating transient single-strand nicks to allow unwinding for DNA replication and RNA transcription.

  • promotes movement of the replication fork and provides genomic stability.
  • once replication complete, religates DNA strands
30
Q

vinca alkaloids

A

vinCRistine
vinBLastine
Vinorelbine

31
Q

vinca alkaloids MOA

A
  • disturb MT formation

- other mechanisms also prob involved (DNA, RNA, protein synthesis, inhib glycolysis, etc)

32
Q

vinca alkaloids w/ significant neuropathy

A

vinCristine

33
Q

vinca alkaloids w/ significant myelosuppresion

A

vinBlastin

34
Q

vincristine uses

A

non-hodgkins lymphoma

ALL

35
Q

vinorelbine uses

A

NSCLC

breast cancer

36
Q

vinblastin uses

A

Hodgkin’s disease

testicular cancer

37
Q

taxanes MOA

A

enhances MT polymerization

can’t break down, blocks cell cycle @ metaphase/anaphase transition

38
Q

taxanes

AE

A
  • myelosuppression
  • neuropathies
  • infusion-related rxns
  • hand-foot syndrome (docetaxcel)

Emma Heme/Onc (16 decks)

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