Antitumor Antibiotics Flashcards

1
Q

Antitumor Antibiotics are produced by

A

Streptomyces bacteria

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2
Q

Antitumar Antibiotic Drugs

A
o	Doxorubicin
o	Daunorubicin
o	Bleomycin
o	Dactinomycin
o	Mitomycin
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3
Q

Antitumor Antibiotics Functions

A

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

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4
Q

Antitumor Antibiotics Major mechanisms

A

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

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5
Q

Antitumor Antibiotics Specificity

A

CELL CYCLE NON SPECIFIC

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6
Q

Structure of anthracyclines

A

 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

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7
Q

Cardiac Toxicity with anthracyclines

A

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

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8
Q

Cardio-Protective Agent

A

Dexrazoxane (zinecard)

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9
Q

Dexrazoxane (zinecard) Function

A

 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

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10
Q

Doxorubicin Use

A

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

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11
Q

Doxorubicin MOA

A
  • 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
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12
Q

Doxorubicin Drug Interactions

A
  • Barbiturates (phenobarbital) – increased metabolism

* CCB (verapamil) – additive toxicity

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13
Q

Doxorubicin SE

A
  • Cardiovascular
  • GI
  • Genitourinary (red urine)
  • Myelosuppresion
  • Hyperuricemia
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14
Q

Dactinomycin (actinomycin-D) Use

A

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

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15
Q

Dactinomycin MOA

A
  • Intercalates between G-C in DNA

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

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16
Q

***Dactinomycin Dose

A

15 mcg/kg/day

17
Q

Dactinomycin SE

A
  • Abdominal pain
  • Diarrhea
  • Hair
  • Teratogenic
  • Skin irritation
18
Q

Dactinomycin Special Property

A

Vesicant!

19
Q

Mitoxantrone (novaltrone) Use

A

Leukemia, lymphomas, and breast cancer

20
Q

Mitoxantrone MOA

A

• Intercalates DNA and interferes with topoisomerase

21
Q

Mitroxantrone Special Property

A

 Can’t produce free radicals = less cardiotoxicity

 VESICANT

22
Q

Mitomycin (mutamycin) Use

A

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

23
Q

Mitomycin MOA

A
  • Bifunctional alkylating agent

* Produces G-G, A-G intrastrand crosslinks

24
Q

Mitomycin AE

A
  • Congestive heart failure

* Myelosuppression

25
Q

Mitomycin Drug Interactions

A

Vinca alkaloids

26
Q

Bleomycin (blenoxane) Use

A

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

27
Q

Bleomycin Structure

A
  • Forms equimolar complexes with metal ions → free radical formation
  • Active form contains IRON
28
Q

Bleomycin Cytotoxic Activity

A

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

29
Q

Bleomycin AE

A

• MOST PULMONARY TOXIC AMOUNG ALL ANTICANCER AGENTS

30
Q

Define Radiation Re-call

A

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