daunorubicin
Summary
Daunorubicin is an anthracycline chemotherapy agent used primarily in acute leukemias (AML, ALL). It works by intercalating into DNA, inhibiting topoisomerase II, and generating free radicals, leading to DNA strand breaks and apoptosis of rapidly dividing cells. Its major dose-limiting toxicity is cardiotoxicity (dilated cardiomyopathy).
Detail
Daunorubicin belongs to the anthracycline class of antineoplastic antibiotics, structurally and mechanistically similar to doxorubicin. Mechanism of action: (1) intercalates between DNA base pairs, disrupting DNA/RNA synthesis; (2) inhibits topoisomerase II, stabilizing the DNA-enzyme cleavable complex and causing double-strand breaks; (3) generates reactive oxygen species (ROS) via iron-mediated electron transport, contributing to both antitumor effect and cardiotoxicity. It is cell-cycle nonspecific but most effective against rapidly dividing cells. Clinical use: primarily in induction therapy for acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), often combined with cytarabine (7+3 regimen). Pharmacokinetics: administered IV (vesicant—avoid extravasation), metabolized hepatically, excreted in bile. Toxicities: Dose-dependent, cumulative cardiotoxicity (dilated cardiomyopathy, arrhythmias) due to ROS-mediated myocardial injury—dexrazoxane (iron chelator) can be given to reduce this risk. Other toxicities include myelosuppression, alopecia, mucositis, and severe tissue necrosis if extravasated (vesicant). Red-orange discoloration of urine is a benign but notable side effect. Liposomal formulations reduce cardiotoxicity by altering drug distribution. High-yield boards association: anthracyclines (doxorubicin, daunorubicin, epirubicin, idarubicin) = cardiotoxicity + topoisomerase II inhibition + free radical formation; remembered via mnemonic 'rubicin = ruins the heart.'
Sources
- First Aid for the USMLE Step 1 (Pharmacology - Antineoplastics)
- Katzung's Basic & Clinical Pharmacology
- Goodman & Gilman's Pharmacological Basis of Therapeutics
- UpToDate: Anthracycline chemotherapy and cardiotoxicity
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