Anthracyclines (anti-Tumors antibiotics)

Question 1

Anthracyclines (general)

Answer 1

Anti-Tumor antibiotics

• Isolated from soil microbes (streptomyces peucetius)
• Topo II inhibitors
• High affinity DNA intercalation- blocks both DNA and RNA synth.
• Generate semi-quinone free radicals– cardiotoxic
• Bind to cell membranes– change in fluidity and ion transport

Question 2

Doxorubicin

Answer 2

Anthracycline
- IV admin. 
- Metabolized in liver to active metabolite
- ABVD combo tx for Hodgkin Lymphoma
Tox: - Myelosuppression w/ neutropenia
- Mucositis
Cardiotoxicity: 
Acute-- 2-3 days into tx, arrhythmias, conduction abnormalities
Chronic-- Dose dependent cardiomyopathy

Question 3

Daunorubicin

Answer 3

AML treatment, ineffective for solid tumors

Question 4

Idarubicin

Answer 4

• Semi- synthetic analog of daunorubicin

- AML induction therapy w/ Ara-C

Question 5

Mitoxantrone

Answer 5

Anthrcycline

• Binds DNA inducing strand breakage
• Myelosuppression
• N/V, mucositis
• Alopecia
• Blue sclera + fingernails

Question 6

Mitomycin C

Answer 6

• Antibiotic from streptomyces caespitosus
• Requires activation thru reduction
• Acts on tumor cells in a hypoxic environment tat favors reduction
• Potent DNA x-linker thru alkylation
• Active in all cell-cycle phases
  Tox: N/V, HUS

Question 7

Bleomycin

Answer 7

-Glycoprotein Antibiotic from streptomyces verticillus
- Metal binding– forms superoxides O2 and OH
- Arrests cells in G2 phase
- IV, IM or SubQ admin
- Renal excretion
Tox: Pulmonary fibrosis