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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
Cardiac Toxicity of Doxorubicin mitigation
``` prolonged infusion Lifetime dose ( ```
26
When is Doxorubicin counter indicated
Not normal cardiac function to start Context of radiation Other cardiotoxic drugs
27
Etoposide DLT
myelosuppression
28
Etoposide clinical
SMALL CELL CARCINOMA OF LUNG GERM CELL TUMORS Aggressive lymphomas broad spectrum
29
Etoposide and leukemia
causes acute leukemia at 1 to 3 per thousand at a 2 to 3 year latency. Characteristically rapid and fatal.
30
Etoposide MOA
Topo II inhibitor
31
what else is given with Irinotecan
loperamide (to bypass diarrhea)
32
Anthracycline problem
damage heart at a proportional level to lifetime dose
33
anthracycline uses
``` Breast cancer AML Lymphoma Small Cell cancer ovarian cancer sarcoma ```
34
Vinca alkaloids MOA
inhibit tubulin POLYMERIZATION and cause mitotic arrest
35
Vinca alkaloids general DLT
Neuropathy (long axon transport sensitive to microtubule disruption)
36
Vincristine
NOT myelosuppressive (added to many regimens)
37
Vinblastine
``` Extremely constipating (think Blast as constipating) ```
38
Taxane MOA
binds to inner surface of microtubule where GDP binds to beta subunit Stabilizes PREVENTS DEPOLYMERIZATION
39
Taxane DLT
Neuropathy
40
Taxane use
Broad
41
Most common used chemotherapy for solid tumors?
Carboplatin and paclitaxel
42
Eribulin
Binds to + end of microtubule preventing ELONGATION
43
Eribulin DLT
myelosuppression, though Neuropathy is real problem
44
Anti-microtubule DLT
NEUROPATHY
45
How many proteosome inhibitors are there
hundreds, 3 FDA approved
46
3 clinically important proteosome inhibitors
Bortezomib Carfilzomib Ixazomib
47
Proteosome inhibitor mechanism
serine protease biochemistry
48
Bortezomib MOA
blocks 26s proteasome proteolytic activity (threonine protease) slow off inhibitor, enzyme essentially dead
49
How to give Bortezomib?
IV or IM
50
How long does Bortezomib dose last
24 hours after single dose
51
Bortezomib DLT
Fatigue Neuropathy Myelosuppression
52
Bortezomib uses
Myeloma | B cell malignancies

IHO Week 3 (4 decks)

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