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IHO Week 3 > Chemotherapy III > Flashcards

Chemotherapy III Flashcards

1
Q

Irinotecan

A

Topo I inhibitor

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2
Q

Daunorubicin
Doxorubicin
Etoposide

A

Topo II inhibitors

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3
Q

Vinblastine
Vincristine
Vinorelbine

A

Vinca alkaloids (anti-tubule)

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4
Q

Length of human genome

A

1.8 m long, nucleus is 6 microns

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5
Q

Topo I

A

Cuts 1 strand DNA

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6
Q

Topo II

A

Cuts 2 stands DNA

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7
Q

Camptothecins

A

Camptothecin
Irinotecan
Topotecan

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8
Q

What is Camtothecins MOA?

A

Natural products that inhibit Topo I

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9
Q

Irinotecan active metabolite

A

SN-38, liberated by ubiquitous hydrolytic enzymes inside or outside of the cell

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10
Q

Irinotecan excretion

A

conjugated to sugars via p450 and excreted into bile

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11
Q

Irinotecan in gut

A

gut flora convert back to SN-38 - results in diarrhea

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12
Q

Irinotecan in blood

A

hydrolyzed back in marrow - neutropenia

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13
Q

Irinotecan MOA

A

Inhibits RE-LIGATION of Topo I activity
Prodrug of SN-38
relies on intact Lactone ring for activity

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14
Q

Irinotecan clinical use

A 
GI cancers (esophagus to colon)
Pancreas
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15
Q

Irinotecan DLT

A

severe diarrhea

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16
Q

Irinotecan and Neutropenia

A

not cumulative and can be given for extended periods in time (> 1 year)
Does not erode cells so that new marrow can’t come back

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17
Q

What is the first thing you think of with Doxorubicin

A

CARDIAC TOXCITY - lowers LVEF

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18
Q

Doxorubicin class

A

Prototype of anthracyclines

Planar with pi electrons

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19
Q

Doxorubicin MOA

A

Topo II stabilizer after it has broken DNA for replication
Prevents DNA helix from being resealed
Stops replication
(gets in nucleus and inhibits Topo II)

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20
Q

Doxorubicin site of action

A

Intercalates into DNA by pi stacking, specifically GC pairs

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21
Q

Why is Doxorubicin toxic?

A

Generates ROS

Loss of Ca/Fe homeostasis - cell death to cardiomyocytes

22
Q

How can you bypass Doxorubicin toxicity?

A

Iron chelators

23
Q

Doxorubicin clinical use

A

BROAD spectrum

24
Q

Doxorubicin DLT

A 
stomatitis (worse by prolonged infusion)
myelosuppression
Nasty vesicant (why given via central line)
25
Q

Cardiac Toxicity of Doxorubicin mitigation

A 
prolonged infusion
Lifetime dose  (
26
Q

When is Doxorubicin counter indicated

A

Not normal cardiac function to start
Context of radiation
Other cardiotoxic drugs

27
Q

Etoposide DLT

A

myelosuppression

28
Q

Etoposide clinical

A

SMALL CELL CARCINOMA OF LUNG
GERM CELL TUMORS
Aggressive lymphomas
broad spectrum

29
Q

Etoposide and leukemia

A

causes acute leukemia at 1 to 3 per thousand at a 2 to 3 year latency. Characteristically rapid and fatal.

30
Q

Etoposide MOA

A

Topo II inhibitor

31
Q

what else is given with Irinotecan

A

loperamide (to bypass diarrhea)

32
Q

Anthracycline problem

A

damage heart at a proportional level to lifetime dose

33
Q

anthracycline uses

A 
Breast cancer
AML
Lymphoma
Small Cell cancer
ovarian cancer
sarcoma
34
Q

Vinca alkaloids MOA

A

inhibit tubulin POLYMERIZATION and cause mitotic arrest

35
Q

Vinca alkaloids general DLT

A

Neuropathy (long axon transport sensitive to microtubule disruption)

36
Q

Vincristine

A

NOT myelosuppressive (added to many regimens)

37
Q

Vinblastine

A 
Extremely constipating
(think Blast as constipating)
38
Q

Taxane MOA

A

binds to inner surface of microtubule where GDP binds to beta subunit
Stabilizes
PREVENTS DEPOLYMERIZATION

39
Q

Taxane DLT

A

Neuropathy

40
Q

Taxane use

A

Broad

41
Q

Most common used chemotherapy for solid tumors?

A

Carboplatin and paclitaxel

42
Q

Eribulin

A

Binds to + end of microtubule preventing ELONGATION

43
Q

Eribulin DLT

A

myelosuppression, though Neuropathy is real problem

44
Q

Anti-microtubule DLT

A

NEUROPATHY

45
Q

How many proteosome inhibitors are there

A

hundreds, 3 FDA approved

46
Q

3 clinically important proteosome inhibitors

A

Bortezomib
Carfilzomib
Ixazomib

47
Q

Proteosome inhibitor mechanism

A

serine protease biochemistry

48
Q

Bortezomib MOA

A

blocks 26s proteasome proteolytic activity (threonine protease)
slow off inhibitor, enzyme essentially dead

49
Q

How to give Bortezomib?

A

IV or IM

50
Q

How long does Bortezomib dose last

A

24 hours after single dose

51
Q

Bortezomib DLT

A

Fatigue
Neuropathy
Myelosuppression

52
Q

Bortezomib uses

A

Myeloma

B cell malignancies

IHO Week 3 (4 decks)

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