Antitumor Antibiotics

Question 1

Antitumor Antibiotics are produced by

Answer 1

Streptomyces bacteria

Question 2

Antitumar Antibiotic Drugs

Answer 2

o	Doxorubicin
o	Daunorubicin
o	Bleomycin
o	Dactinomycin
o	Mitomycin

Question 3

Antitumor Antibiotics Functions

Answer 3

o Intercalation (insertion) between base pairs (doxorubicin)
o DNA strand fragmentation (bleomycin)
o Cross-linking the DNA strands (mitomycin)
o Overall they inhibit DNA replication and RNA synthesis

Question 4

Antitumor Antibiotics Major mechanisms

Answer 4

 Topoisomerase II inhibition through DNA intercalation
• Can cut but not ligate
 Free radical generation
 Inhibition of signal transduction pathways

Question 5

Antitumor Antibiotics Specificity

Answer 5

CELL CYCLE NON SPECIFIC

Question 6

Structure of anthracyclines

Answer 6

 Have a tetracycline ring + sugar (daunosamine) attached by glycosidic linkage
 Also have quinone moieties which accept electrons that forms the hydroxyl quinone which makes the drug unstable and then gives said electron away to oxygens for ROS production

Question 7

Cardiac Toxicity with anthracyclines

Answer 7

Semiquinone and hydroxyquinone can return to quinone form by donating the electron to oxygen or hydrogen peroxide to form hydroxyl radical which cause DNA damage and lipid peroxidation → desoty the cardiac myocytes

Question 8

Cardio-Protective Agent

Answer 8

Dexrazoxane (zinecard)

Question 9

Dexrazoxane (zinecard) Function

Answer 9

 Undergoes hydrolysis and accepts the iron from the anthracycline- iron complex and the regeneration of the free doxorubicin
 Prevents the formation of the iron version
 Given BEFORE doxorubicin administration

Question 10

Doxorubicin Use

Answer 10

carcinomas, carcomas, hematologic cancers (leukemia, hodgkin’s)

Question 11

Doxorubicin MOA

Answer 11

• Binds directly to DNA via intercalation between base pairs
• Inhibits topo II which blocks DNA and RNA synthesis and fragmentation of DNA
• Iron-chelator: this complex can bind DNA and membranes better and produce free radicals that immediately cleave DNA

Question 12

Doxorubicin Drug Interactions

Answer 12

• Barbiturates (phenobarbital) – increased metabolism

* CCB (verapamil) – additive toxicity

Question 13

Doxorubicin SE

Answer 13

• Cardiovascular
• GI
• Genitourinary (red urine)
• Myelosuppresion
• Hyperuricemia

Question 14

Dactinomycin (actinomycin-D) Use

Answer 14

rhabdomyosarcoma, eqings sarcoma and wilm’s tumor (kidney cancer)

Question 15

Dactinomycin MOA

Answer 15

• Intercalates between G-C in DNA

* Dactinomycin-DNA complex blocks transcription of DNA by RNA polymerase

Question 16

***Dactinomycin Dose

Answer 16

15 mcg/kg/day

Question 17

Dactinomycin SE

Answer 17

• Abdominal pain
• Diarrhea
• Hair
• Teratogenic
• Skin irritation

Question 18

Dactinomycin Special Property

Answer 18

Vesicant!

Question 19

Mitoxantrone (novaltrone) Use

Answer 19

Leukemia, lymphomas, and breast cancer

Question 20

Mitoxantrone MOA

Answer 20

• Intercalates DNA and interferes with topoisomerase

Question 21

Mitroxantrone Special Property

Answer 21

 Can’t produce free radicals = less cardiotoxicity

 VESICANT

Question 22

Mitomycin (mutamycin) Use

Answer 22

Anal, bladder, colon, gastric, and head and neck cancers

Question 23

Mitomycin MOA

Answer 23

• Bifunctional alkylating agent

* Produces G-G, A-G intrastrand crosslinks

Question 24

Mitomycin AE

Answer 24

• Congestive heart failure

* Myelosuppression

Question 25

Mitomycin Drug Interactions

Answer 25

Vinca alkaloids

Question 26

Bleomycin (blenoxane) Use

Answer 26

hodgkin’s disease, testicular cancer, head/neck cancer, cervical cancer, kaposi’s

Question 27

Bleomycin Structure

Answer 27

• Forms equimolar complexes with metal ions → free radical formation
• Active form contains IRON

Question 28

Bleomycin Cytotoxic Activity

Answer 28

• Causes oxidative damage ot the deoxyribose of the thymidylate leading to single and double stranded breaks in DNA which inhibits DNA synthesis

Question 29

Bleomycin AE

Answer 29

• MOST PULMONARY TOXIC AMOUNG ALL ANTICANCER AGENTS

Question 30

Define Radiation Re-call

Answer 30

If the patient gets radiation treatment in a different part of the body, the radiation and the drug can interact and cause inflammation in a different part of the body