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Chemotherapeutic Antibiotics
Anthracyclines
Summary
- Doxorubicin is the most widely used, and is commonly referred to as the “Red Devil” because of its eye-opening red pigment and cardiotoxicity: all of the anthracyclines can produce cardiotoxicity through free radical formation.
- It classically and commonly taught that doxorubicin produces irreversible (type I) cardiotoxicity (dilated cardiomyopathy) and trastuzumab produces reversible (type II) cardiotoxicity, but on deeper inspection each can do the opposite: aspects of anthracycline toxicity is reversible and some of the cardiotoxicity from trastuzumab can be irreversible.
- The cardio-pathology from anthracyclines is multifactorial, it’s helpful to consider that, in part, it stems from the same pathogenesis as with neoplastic cells: DNA damage and free radical-induced apoptosis.
- Trastuzumab cardiotoxicity likely involves antibody-mediated cytotoxicity or cell death directly related to its primary mechanism of action: the inhibition of HER2 signaling pathways.
- Daunorubicin was the first anthracycline to be used in the treatment of cancer.
- Mitoxantrone is an anthracycline analogue, (it’s actually an anthracenedione), which can cause blue discoloration to the nails, as well as the urine and sclera. Its primary dose-limiting side effect is myelosuppression.
Mechanisms
- The anthracyclines have multiple anti-neoplastic mechanisms of action, including DNA intercalation (wedging themselves between DNA base pairs to disrupt DNA structure); topoisomerase II inhibition; and free radical formation.
- DNA intercalation works as follows: the chemotherapy inserts itself in between base pairs,
Miscellaneous
- Mitomycin, which acts via alkylation, and can cause pulmonary fibrosis.
- Bleomycin is an antitumor antibiotic that produces DNA breakage.
- Bleomycin forms single and double-strand breaks in DNA; specifically, it forms metallobleomycin complexes that break the 3’-4’ bonds of deoxyribose and, which results in cell cycle arrest in G2.
- A key side effect of this drug is pulmonary fibrosis, presenting with hemoptysis.