Topoisomerase Inhibitors

Question 1

Cancer cells possess more of this enzyme involved in the replication and transcription than normal cells do

Answer 1

topoisomerase

Question 2

these 2 anthracycline antibiotic are natural products of certain soil fungi

Answer 2

doxorubicin and daunorubicin

Question 3

what is the mechanism of action of doxorubicin and daunorubicin

Answer 3

bind to DNA-interfering with the ability of nucleic acids to serve as a template during replication

Question 4

doxorubicin and daunorubicin - their drug induced free radicals overwhelms which organ in the body

Answer 4

hearts

Question 5

1-2 days after administration of daunorubicin and doxorubicin this will be seen in the urine

Answer 5

red urine

Question 6

what occurs with each subsequent dose of daunorubicin and doxorubicin

Answer 6

it diminishes the hearts ability to withstand subsequent oxidant stress

Question 7

explain the mechanism of how doxorubicin and daunorubicin free radicals affect the heart

Answer 7

free radicals overwhelm the hearts antioxidant defenses- leading to oxidation of critical cardiac proteins and membrane components (unsaturated free fatty acids)

Question 8

daunorubicin clinical uses

Answer 8

acute lymphocytic and myelocytic leukemia

Question 9

doxorubicin clinical uses

Answer 9

metastatic adenocarcinoma of the breast
carcinoma of the bladder
bronchogenic carcinoma
metastatic thyroid carcinoma
oat cell carcinoma
osteogenic carcinoma

Question 10

side effects of daunorubicin and doxorubicin

Answer 10

cardiomyopathy and myelosuppression

stomatitis, gastrointestinal disturbances and alopecia are common side effects

Question 11

if cumulative dose of doxorubicin is less than 400mg/m -what percent of patients develop congestive heart failure

Answer 11

3%

Question 12

if cumulative dose of doxorubicin is 700mg/m what percent of patients develop congestive heart failure

Answer 12

18%

Question 13

prior radiation or previous treatment of which drug can increase risk of cardiomyopathy

Answer 13

cyclophosphamide

Question 14

2 months after cessation of treatment with doxorubicin “this” has been described during general anesthesia

Answer 14

acute left ventricular failure

Question 15

describe some characteristics of the acute form of cardiomyopathy that can occur with doxorubicin

Answer 15

st - t changes
decrease QRS voltage
PVC's
SVT
cardiac conduction abnormalities
left axis deviation 
acute REVERSIBLE decrease in the ef within 24hrs after a single dose

Question 16

what dose levels can the acute form of cardiomyopathy

Answer 16

ALL dose levels

Question 17

describe some characteristics of the insidious(gradual) onset of cardiomyopathy

Answer 17

dry nonproductive cough-suggesting bronchitis

rapidly progressive heart failure-unresponsive to inotropic drugs and mechanical ventricular assistance.

Question 18

the insidious onset of cardiomyopathy is fatal how many weeks after onset of symptoms in 60% of patients

Answer 18

3 weeks!

Question 19

are there predictive test to determine early recognition of impending cardiomyopathy

Answer 19

no

Question 20

what is the free radical scavenger that protects the heart from doxorubicin-associated damage

Answer 20

dexrazoxane

Question 21

increased plasma concentrations of ____reflect drug induced injury to myocardial cells

Answer 21

troponin T

Question 22

what is the clinical use of dactinomycin

Answer 22

wilms tumor in children

rhabdomyosarcoma

Question 23

how does dactinomycin work

Answer 23

binds to DNA -RNA polymerase and transcription of the DNA molecule is blocked.

Question 24

dactinomycin can be used to inhibit immunologic responses as with what situation

Answer 24

organ transplant

Question 25

side effects of dactinomycin

Answer 25

nausea, vomiting, myelosuppression manifestation as pancytopenia

Question 26

bleomycin moa

Answer 26

produces free radicals which create DNA breaks

Question 27

bleomycin is administered IV and high concentrations occur in what two spots

Answer 27

skin and lungs

Question 28

bleomycin in combination with vinblastine is used to treat

Answer 28

testicular carcinoma

Question 29

what is bleomycin useful in the palliative treatment of

Answer 29

squamous cell carcinoma of the head, neck, esophagus, skin, and genitourinary tract

Question 30

what are the MOST COMMON side effects of bleomycin

Answer 30

mucutaneous reactions, stomatitis, alopecia, pruritus, erythema, hyperpigmentation.

Question 31

what does bleomycin cause for myelosuppression

Answer 31

MINIMAL myelosuppression

Question 32

what three things seen during an acute reaction in patients with lymphoma receiving bleomycin

Answer 32

hyperthermia hypotension hypoventilation

Question 33

what is the most serious side effects of bleomycin

Answer 33

dose related pulmonary toxicity

Question 34

what inactivates bleomycin- which is deficient in lung tissue

Answer 34

hydrolase enzyme

Question 35

what are the first signs of pulmonary toxicity from bleomycin

Answer 35

cough, dyspnea, basilar rales

Question 36

name the 8 risk factors for development of chemotherapy-induced pulmonary toxicity

Answer 36

``` total drug dose age concurrent or prior chest radiation oxygen therapy combination chemotherapy preexisting pulmonary disease genetic predisposition cigarette smoking ```

Question 37

what is the recommended inhaled oxygen concentrations for bleomycin treated patients

Answer 37

less than 30%

Question 38

some reports state that oxygen concentrations greater than 30% can be harmful how many many after last dose of bleomycin

Answer 38

6-12mo

Question 39

does corticosteroid pretreatment in patients whom have a greater risk of needing more than 30% oxygen prove helpful?

Answer 39

not confirmed

Question 40

how do we fluid replace patients with bleomycin treatment

Answer 40

give colloids over crystalloids.